Game Breaker / Enter the Gungeon

Though it's difficult to pick up worthwhile synergies as compared to other rogue-likes, some items are ridiculous enough on their own; and the few synergies that exist — official or otherwise — can make the game a cakewalk.

• Ancient Hero's Bandana quadruples ammo on all of your guns. That's crazy enough, as you can not only go wild with your shooting, but now all these Awesome, but Impractical weapons with low ammo counts become so much better; however, combined with Black Hole Gun — which, as you might expect, summons a black hole that sucks in all incoming bullets and draws enemies in — it nullifies any danger from High Dragun or The Lich; 120 black holes is enough to weather down them with little trouble.
• Casey and the Alien Engine can rack up obscene amounts of damage quickly, the former hitting as hard as the AU gun and just as hard if you knock back lots of bullets, and the latter has a ridiculous fire rate, alongside setting enemies on fire. The problem is that these weapons are balanced by not being ranged, and the engine blows you backward, which can be dangerous against foes like Treadnaught. Enter the Flak Bullets. Both weapons now fire tiny pellets that pack the same punch as before. Plus, the Alien Engine comes with 1100 shots and Casey has infinite ammo, so you are free to go nuts with shooting your newly overpowered weapons. Furthermore, the recoil from firing the Alien Engine is completely removed if you find the Heavy Boots, letting you spam it and melt anything that comes close to you.
• AKEY-47 is a fancier AK-47, a respectable gun, but rather disappointing for an S-quality item... except AKEY opens chests. A single bullet unlocks it without you needing to spend a key on what might potentially be a bad item, letting you hoard keys for Flynt and ensuring you get everything you can. The Shelleton Key, which is just as rare, does the same thing as a passive item, and if you somehow manage to come across both items, the AKEY-47 gains a significant damage multiplier and infinite ammo. As stated before, the weapon is already respectable, so you will practically need no other weapon for the run.
• Muscle Relaxant used to reduce the spread of all weapons by two thirds and triple the damage of rifle-based weapons, making even fairly lackluster guns like Crossbow or Hegemony Rifle formidable weapons. It, however, possessed a separate synergy with Sniper Rifle and Hexagun, on top of the one already provided; a bonus 50% increase in damage for a whopping total of 450% more damage. It's proven too good and Muscle Relaxant lost the tripled damage after Supply Drop update, instead offering the 50% damage boost to a wider selection of guns.
• Makeshift Cannon is a one-shot only weapon that does an obscene amount of damage and ignores bosses' damage cap. That sounds scary enough, but giving it only a single bullet makes it more reasonable, right? Here comes the Duct Tape, a one-use item that lets you combine two guns into one that shoots both with combined ammo count. Combine it and another weapon with large ammo to obliterate enemies as you please.
• The Mahoguny is absurdly practical for a C grade gun. It is, in essence, a wooden grenade launcher, three times as powerful as your starting gun. But allow us to list what else it can do. Its shots bounce off walls. It fires several leaves along with it that also do damage to people hit by it. It has a magazine size of TEN. It holds 350 rounds, or 385 if you play as The Pilot. It has very little spread comparatively. The explosions destroy enemy bullets. The explosions do not hurt you. It possesses several very useful synergies with other weapons, most notably with decoys/Heavy Boots/Broccoli which lets it fire three explosive rounds at once. And lastly, simply firing the thing makes a wonderful, distinctive noise. Any 2-3 of those qualities would have made it a practical weapon, but all of those combined make it an all-purposes gun that, unless you are extremely unlucky with drops or woefully inaccurate, pretty much never runs out of ammo. The only real downsides it has is that it cannot pierce scenery objects such as pots and crates, and it isn't effective at locating secret rooms. Also, to reiterate: This is a C Grade gun, meaning it can drop from the second-lowest tier of chest, even on the first level.
• The Fossilized Gun. Deals little damage by just shooting, but covers the area in gasoline and you can set it on fire with your reload. Put simply, it's a fantastic room clearer.
  • One up from this - the Mega Douser has a similar and arguably safer synergy with one of the hidden playable classes, the Robot. It starts with the Battery Bullets passive, which electrifies all bullet-based projectiles, and is also immune to shock damage from water puddles, unlike other characters. The Mega Douser is a super soaker that drenches the room with massive puddles of water. Electrified water deals constant damage to all grounded enemies. You do the math. The only downside is that it doesn't hit airborne enemies, but since you aren't relegated to a tiny spot in the room, you can pick them off easily, especially with the hidden accuracy bonus given by Battery Bullets.
  • One upping this even FURTHER is the Starpew, a watering can that can be charged up and fired in clusters. This might seem lackluster considering the gun's high tier, but a single shot fires 18 bullets that do decent damage, if fully charged. And of course, said bullets also leave water puddles when they successfully hit an enemy, which combined with Battery Bullets, means grounded enemies are guaranteed to take electric damage on top of whatever damage the bullets already dealt!
• The Yari Launcher, a minigun that fires homing rockets. By itself it can easily curbstomp early bosses and deal heavy damage to later ones due to being one of a precious few weapons in the game that ignores the boss DPS cap, likely allowing the player to avoid getting hit and scoop up a precious health upgrade along the way. If playing as either The Pilot or The Marine, however, this gun becomes 100% better. The Pilot's special abilities let him carry extra ammo and buy ammo from shops cheaper, making it much easier to stock up for tough encounters and bosses. As for The Marine, he doesn't get the extra magazines The Pilot does, but he doesn't need them, since his active item gives him a single free resupply anytime he wants. If used correctly, this lets the player bypass an additional boss (likely earning another health upgrade in the process) or an entire level with minimal danger. On top of all that, if you happen to have the Oiled Cylinder, the gun gains a synergy that boosts its damage output even further and increases its clip size to 30 rockets per mag. While the Yari Launcher usually isn't enough to outright win the game by itself it gives players a BIG push towards victory, especially if found early on.
• The Ring of Triggers is an awesome item, especially if you have an Active Item that has no cooldown like the Jetpack, and has the potential to be broken with several weapons. As the item fires your current gun multiple times clockwise without consuming ammo when an Active Item is used it can make several rooms in the game a joke. Have the Makeshift or Glass Cannons? Enjoy one shotting bosses if combined with an item that gives their shots bouncing too.
• While the chances of finding it in the shop are low, the Drill is comparible to the AKEY-47 and Shelleton Key. It can unlock all chests just without keys, which is godsend. What really makes the Drill shine is that it's a D rank item, so it won't hurt the chances of finding another amazing item. While you can be placed in pretty nasty battles with the usage of the drill on S and A chests, you'll probably have a stockpile of keys at this point.
• Stumbling upon the Clone item on any given run will practically give you a guaranteed victory. Instead of dying, you restart at the first room of the Gungeon... but with all your items still. This means a second chance to scoop up as much loot as you possibly can, decimate early level bosses (and take their Mastery Rounds, which will stack with themselves for obscene amounts of health), and utterly curbstomp the Dragun. And yes, you can get another Clone on a repeat run.
• Finding all four of the Gunknight armor pieces transforms you into Cormorant, the Aimless Knight, and removes reload times for all guns, allowing you to spam high-damage weapons that normally have small or one-bullet clips like the Grasschopper or the AU Gun and rinse most bosses. Even better, finding one piece increases the likelihood you'll find another on that run.
  • Similarly, finding all four of the Resourceful Rat's items turns you into the pest. His items are pretty strong regardless, especially the Elimentaler, but with all four items, the rat will stop stealing your items and guns! Ammo and armor will remain untouched for the remainder of the run, too. Unlike the knight, you can always find the items in a run if you can survive the Rat boss fight and beat the Punch-Out section using star punches. All in all, every gungeoneer's dream has been realized.
• The Gungine is a fast-firing, S-tier weapon that grants the player a huge movement speed boost, and when reloaded while standing on top of a patch of liquid, completely refills any spent ammo. This is normally balanced out by its total ammo capacity of 800 rounds and using 100-round clips... unless you find the Bug Boots, an item that grants poison immunity and creates a trail of poison at the player's feet when they dodge roll. Played right, this gives you infinite ammunition on an extremely powerful weapon with a ridiculous fire rate and a passive movement speed boost. You will never need to use any other gun on that run if you get lucky enough to find these two items together.
  • Even better, it's not the only item that can do that. Any liquid-creating weapon like Mega Douser, Fossilized Gun or Mutation can be used to fuel the Gungine, once you realize that while weapons do reload automatically when you change them, it doesn't happen if you change back fast enough. And if you have the Devolver, the Gungine gains a synergy where all killed enemies leave pools of oil behind, letting it indefinitely fuel itself.
• The "Advanced Gungeons and Draguns" update added a lot of synergies between chest items, with their usefulness ranging from 'neat little sidegrade' to 'infinitely more deadly.' Apart from the ones mentioned above, here are a few more notable ones:
  • The Machine Pistol's viability is much greater when combined with high-tech items such as Fortune's Favor or the Bionic Leg, gaining increased damage and an electric chaining effect between bullets.
  • The Great Queen Ant synergy for the Gungeon Ant, obtained through having said weapon plus either a crown-based item such as Gilded Bullets, the Heck Blaster or the Ring of Fire Resistance, shoots high-velocity, damaging rockets that block bullets, turning it from a subpar flame weapon that's difficult to use into essentially the most viable rocket launcher in the game.
  • The Heroine is already a great B-tier charging weapon, but its synergies with Frost Bullets, Hot Lead and Shock Rounds allows one to access alternate fire modes that, respectively, freeze enemies almost instantaneously with fully-charged shots, fire giant piercing fireballs and double wave shots connected by electricity. If that isn't enough, the Pig item also possesses its own synergy which quadruples the Heroine's damage when the player is revived, an extra shout out to the end of Super Metroid. To put it bluntly, whatever foe you happened to die to at the time will be in for quite the reckoning.
  • Any room with a table in it becomes infinitely easier to clear when you have both Table Tech Sight and the Bloody Eye/Liquid Valkyrie, because flipping them while holding the two items stops time completely for several seconds, on top of the triple-shot bonus you normally get from the former. Becomes even more ridiculous, naturally, with the Portable Table Device item, which allows you to trigger this effect on demand, albeit only three times max before a short cooldown period.
  • The Buzzkill fires buzzsaws at high velocity that bounce around the room. A fairly respectable C-grade gun in its own right, but if you manage to find a Regular Shotgun/Winchester/Rattler, the sawblades become chained together with pink lightning and travel much slower, hitting targets way more frequently and letting you clear out smaller rooms without even having to aim.
  • If you find Brother Albern in a secret room and destroy his unique chest, you obtain a "Lies" junk, which is useless on its own. However, it synergizes with the average-strength Betrayer's Shield and turns it into a fast-firing superweapon with infinite ammo, in addition to its standard effect of producing a barrier upon reloading. This is less likely to get than other synergies, but you're guaranteed to find Brother Albern in the secret room of the Abbey of the True Gun if your run passes through there. A similar infinite ammo synergy exists between the AKEY-47 and Shelleton Key.
• The Elimentaler may very well be the almighty king of broken guns. In addition to having infinite ammo, it also fires rapid shots that quickly encase enemies in cheese, freezing them solid. Furthermore, enemies that are killed with this weapon release a large spread of cheese creep onto the floor, which encheeses other enemies when stepped on. The only drawbacks for this gun are its difficult unlock requirements, which involve finding and defeating the Resourceful Rat and getting lucky enough to find it in one of his reward chests, and its inability to find secret walls, which becomes moot as you can hoard ammo for weapons that are better suited for that purpose. Talk about a weapon that cheeses the game...
• Blasphemy, the starting weapon of The Bullet, is a sword that doesn't require any ammo and can erase any bullets or special attacks flying at you with a single swing - in a game where dodging bullets is the primary challenge. That, and the fact that it also shoots relatively powerful projectiles when your character has full health. At worst, it's a simple way to rack up heart containers on easy master rounds; at best, it can turn even the end-game boss fights into a cakewalk when used properly.
• The Platinum Bullets are incredibly simple and incredibly powerful. They permanently increase the power and firing speed of all your guns every time you hit an enemy. This caps out at 3x damage and firing speed, allowing even starter guns to be competent room clearers well into a run. The more powerful weapons you pick up during a run just get overtuned to hell and back, allowing you to potentially win the run on just one gun that might otherwise be good but not overwhelming on its own.
• Also in bullet mods, Blank Bullets. These allow shots to set off short-range blanks when they impact an enemy. As long as it's not a beam weapon, the Blank Bullets can make any gun capable of completely stuffing most enemies. It's especially comical on any weapon that fires incredibly quickly, as it means the Blank Bullet effect will be proccing nearly all the time and erasing all the enemy's attacks. Also recall that Ammolets will activate whenever any blank effect is used...including the Blank Bullets. Grab one of those and you can deal even more damage and mess with entire rooms of enemies just by focusing down one of them. Being able to find hidden rooms for free is just the cherry on top of this ridiculous sundae, really.
  • This then becomes even more borked with the Elder Blank. Having Blank Bullets with the Elder Blank will cause enemy bullets to reflect back towards enemies, (without damaging the player) meaning that (assuming you have Ammolets) you can be simultaneously melting an enemy, erasing their projectiles, dealing radial status effects, andreflecting their attacks back towards them.
  • Blank Bullets shine the most with rapid-fire automatic guns - and it doesn't get better in that department than Heck Blaster, a B-tier gun with a massive ammo count and hitscan bullets. You can neuter any enemy in the game as you please.
• The final playable Gungeoneer added in the Farewell to Arms update, the Gunslinger. His gun, the Slinger, is merely good, being an above-average pistol with a free stun on reload from empty, but that's not what makes him broken. No, his starting passive item, the Lich's Eye Bullets, gives him every synergy for every gun he picks up, for free. Now, it has flaws: it only grants the guns' part of synergies, and none of the other effects based on active or passive items, and some weapons' synergies will override others (sometimes not for the better, and sometimes can cause problems with some weapons such as the Quad Laser) or not work together (for example, Dual Wielding won't work, even if you have both guns), but it still turns even low-tier guns into ridiculous Infinity +1 Guns that stack up to some S-tier guns...which themselves become ludicrously overpowered, as well. It's little wonder, then, that even so much as playing him costs Hegemony Credits once he's unlocked.
• Chamber Gun is a gun that changes forms depending on what chamber you're in, and most of them are pretty mediocre...unless you take it to Bullet Hell and it becomes the strongest homing weapon in the game, able to clear rooms with only a a couple of it's 500 ammo, and crush the Lich with ease.
• Gunther. As your weapon unlock for beating Challenge Mode, he seems rather underwhelming at first glance, with his main problem being his inaccuracy. His main draw is that clearing rooms using him makes him power up more and more, until he's essentially a super-gun that deals lots of damage really fast with crazy sharp homing projectiles. Combined with his infinite ammo, he's an amazing weapon to clear rooms with, and great at killing bosses.
• The game has a hidden "Magnificence" stat that increases every time you find an A- or S-ranked item. Each time the game generates a new item, your Magnificence is checked to determine the chance for the item to be re-rolled without the possibility of being A or S rank. This greatly limits the number of these premium items you can find in one run; after encountering two, any further A/S chests have a 95.53% chance of turning into something of lower quality - and that's without considering their normal rarity. Enter the Seven-Leaf Clover. This item not only overrides the Magnificence re-roll, it forces the opposite: turning every chest at floor generation into a red or black chest. Along with decreasing the reload time of the Wind Up Gun. Want one of those Game Breakers listed above? Why pick, when you can have all of them?
• Similar to the above, Bowler's Rainbow Runs. The downside? You can't get loot from chests of any quality other than rainbow, nor gain any weapons or items in any other normal way. The upshot? You don't need to, because Bowler supplies a rainbow chest every floor, essentially granting you a choice of at least one A-or-S-tier item for free, in addition to freeing up the money you'd usually spend on keys to open chests so that you can buy hearts, blanks, and ammo. Aforementioned Game Breakers like the Clone show up shockingly often, and while the mode doesn't ensure victory, it'll very often lead to it.
• Black Hole Gun and the Abyssal Tentacle have an incredibly strong Synergy. The black holes will suck in bullets while firing three tentacles that heavily damage any enemy on screen. This synergy shines in bullet hell, giving a combination of offense and defense that only gets better with passives that increase damage.
• The Knight's Gun will dig into the ground after reloading with an empty clip, granting a pickup. Spice increases damage (at the cost of wider spread, reduced health, and curse), as well as replacing future pickups with Spice. Including the pickups from the Knight's Gun. The damage boosts will stack to where even though you only have one heart, the enemies won't live long enough to damage you.
• The Wood Beam is just a plain ol' 2x4, but is deceptively powerful for a B rank "gun". "Firing" the Wood Beam merely stretches it out to your cursor's location. Its damage isn't normally impressive if you use it like a standard gun, but it can outright decimate room after room if you flail your cursor around fast enough, as the damage dealt by the beam is dependent on how fast you swing it into an enemy. It also happens to ignore walls, so saddling yourself up next to a pillar for cover makes it near impossible for enemies to approach without getting smacked to death. If it wasn't for the boss DPS cap, you could kill any of them in a matter of seconds.
• Casey, in the right hands, can effortlessly obliterate just about any challenge in the game. Not only is it capable of instantly killing most enemies you'll run into, it deflects bullets. When used at the right time, it can turn some of the most powerful attack patterns in the game into massive liabilities for the bosses that use them. This also leaves easily-exploitable openings in said attack patterns, turning them into a cakewalk to dodge through. This, in turn, means that racking up Master Rounds becomes easy, which in turn makes you even harder to kill. You're also free to cherry-pick stat-boosting items, since you have absolutely no need whatsoever to pick up any other weapon once you get Casey.
• The Full Metal Jacket automatically uses blanks whenever the player would have taken damage (including non-bullet damage like bottomless pits), negating it. Blanks are pretty easy to stockpile compared to health or armor, and the auto-blank makes completing No Damage Runs like getting Master Rounds considerably easier, allowing you to stack up a ton of health in the case that your blanks eventually run out. In general, effectively turning all blanks into armor makes surviving significantly easier, since it's relatively common to mistime blanks or just not use them - it's not uncommon to just never take actual damage for the rest of the run after obtaining the item, even during some tough boss fights.