This trope is the premise of the story of the Silver Surfer. After sacrificing himself to become a slave to a supernatural godlike destroyer of worlds (to save his own homeworld, of course), the hero's memory is taken from him AND his homeworld gets displaced. After he (very quickly into the story) regains his memories, the rest of the plot is largely about finding his home planet again.
A series of Peanuts strips followed Snoopy taking Woodstock to the Daisy Hill Puppy Farm where he (Snoopy) was born, only to find it had been replaced by a parking garage.
Snoopy: You stupid people! You're parking on my memories!!!
Occurs to mutant alligator Leatherhead in Teenage Mutant Ninja Turtles after he is inadvertently left behind on Earth by the escaping Utroms; several stories involve him unsuccessfully trying to reach the Utrom homeworld.
This is the premise of the Legion of Super-Heroes story Legion Lost. A group of Legionnaires find themselves galaxies away from Earth in a thrashed starbase.
Alan Moore wrote a Time Twister for 2000 AD centered around a character, Sideways Scuttleton, who can travel to alternate universes by "wiggling his back in a certain way." Unfortunately, he didn't count on his back going out in his later years, making it difficult to him to return to his own universe. The story is actually a bit of a subversion because when he asks someone for bus fare in a dimension that he's pretty certain is his own, the man produces the British £1 coin which upsets Scuttleton because in his dimension people use paper notes instead of coins; however, the story was written shortly after such coins were first introduced in 1983, and Scuttleton very well may have stumbled into his home dimension without fully realizing it.
The Life and Times of Scrooge McDuck combines this with Stranger in a Familiar Land. Having spent most of his teen and adult life abroad, Scrooge has a great deal of trouble fitting in with the traditional Scottish people. He decides to begin a new life in America, this time bringing his sisters along for the ride.
Used as the in-story reason for Static joining the Teen Titans. He was worried that his family believed him to be dead due to the months he spent in captivity, so he stayed with the Titans for a while until he could work up the nerve to return home and confront his parents.
In Stars Above, Homura's trip from her own time and universe was one-way. Even with her powers, it took a significant boost from another Puella Magi to go back six years, and there's no way to do it again.
Happens to Nanoha in Game Theorywhen she joins Precia, since she can't return home without being captured by the TSAB.
In Sophistication And Betrayal, the protagonist ends up permanently stuck in Equestria after efforts to send him back home fail, resulting in the spell unable to be cast on him again without killing him in the process.
A major element in 2007's Transformers movie.The civil war on Cybertron damaged the planet's surface, and the Allspark being destroyed means that the planet will die eventually. At the end of Transformers: Dark Of The Moon, the Space Bridge's destruction possibly causes Cybertron to collapse on itself, forever preventing the Autobots from returning to their old home.
An American Tail : The reason the Mousekewitz family emigrates to America is because the Cossacks burned their village to the ground.
In Grosse Pointe Blank, John Cusack's charcter, Martin Blank, return to his home town for a reunion. While there, he visits his childhood home, only to find that it's become a convenience store. This causes him to say the line, "You can never go home again, but I guess you can shop there."
In Inception, the sole reason for Cobb to accept the mission is because Saito has enough influence to allow him to return home to his children. He is wanted by the police as the primary suspect for his wife's death and went into hiding, leaving his children behind with their grandparents. In a particularly painful twist to the old plot, his wife believed that the real world was a shared dream of them and that they would have to die to wake up in the real world. So she set up her own suicide making it appear as if he murdered her, directly mentioning that he would no longer be able to return to his family in the supposed dream, in the hope that he would also kill himself so they could both wake up in the real world.
In Star Trek, Spock and Spock Prime both wind up afflicted by this trope: Spock because Vulcan has just imploded and Spock Prime because he's marooned in another timeline...and Vulcan has just imploded.
And, of course, the Big Bad, Nero, is in the same boat, thanks to the supernova that took out Romulus and his subsequent time-traveling.
The Searchers ends with John Wayne leaving because his behavior has alienated his family.
In the Forrest Gump movie, Forrest has Jenny's childhood house razed in order to bring closure to years of abuse by her father.
Paint Your Wagon features this lyric: "Home is made for coming from, for dreams of going to/ which, with any luck will never come true."
In the film version of The Hitchhiker's Guide to the Galaxy, the Earth is restored, but Arthur Dent decides that the world would be a better place without him, having fallen in love with Trillian and wanting to share her wanderlust.
The Hunt for Red October. Marco Ramius makes sure that his defection will be real by burning all of the bridges behind him.
In Idiocracy, where the main characters, after hibernating in pods for 500 years, wake up to a world of naturally selected idiots.
In Harlem Nights (1989), Quick (Eddie Murphy) and Sugar Ray (Richard Pryor) pull The Caper that results in the death of the major rival crime boss.. Knowing the danger of what they have done, they take a last wistful look at the New York skyline before bidding the city goodbye.
The movie Silent Hill after Rose and Sharon leave Silent Hill and apear to arive back home, they are still in another reality because they entered the world of Silent Hill. Thus they can never truely return home.
It takes Columbus a while to come to this conclusion in Zombieland. He wants to get back to Ohio to see if his family is still alive (although he eventually admits that that wouldn't mean much even if they were). He reacts appropriately when Wichita tells him that that's a pretty fruitless venture, as it's "a total ghost town". He still doesn't quite get it until he's about to leave and he realizes that he really can't go back home.
Done in the movie Vamp, when Keith finds his friend AJ.
AJ: You don't get it do you? For me, home is a million miles away now. Home is on another planet. (He hunches over before rising with fangs and gold eyes) I'm a fucking zombie now!
In Madagascar 3: Europe's Most Wanted, Alex and his friends finally make it back to the Central Park Zoo in New York City, only to realize that they have grown to prefer being free after all.
In About Schmidt, during one of his excursions on the way to his daughter's wedding, Schmidt goes to visit his childhood home from many years ago, only to find a tyre shop now standing in its place. He still goes inside and tries to reminisce, to the bemusement of the clerk.
The song "I Can Never Go Home Anymore" by the Shangri-Las is made of this trope. It's essentially An Aesop about a girl who runs away from home and breaks her mother's heart to be with a boy, who she forgets about almost immediately, while it's implied that her mother dies of loneliness in the meantime.
"You Can Never Go Home" by The Moody Blues presents a psychological/spiritual version of the trope.
Burt Bacharach and Hal David's 24 hours from Tulsa, which is as close to home as Gene Pitney gets due to an unplanned encounter at his stop-off, which eventually leads to "I hate to say this to you, but I love somebody new. What can I do? And I can never, never, never go home again."
The Finnish military march Jääkärimarssi (Yeager March). Syvä iskumme on, viha voittamaton, meillä armoa ei, kotimaata (Our strike is deep, our wrath implacable, we have no mercy and no homeland). Makes sense, because the Yeagers were patriots (or traitors, depends on which side you look at) who during the WWI joined the German Army to get military training for liberation war against Czarist Russia. The Czarist Law stated mandatory death penalty from high treason.
The Deep Imaskari race in the Dungeons & DragonsUnderdark setting live in a Hidden Elf Village. If anyone decides to leave, they automatically have the location of their home erased from their memory so that in the (highly likely) chance they are captured by something evil that can read minds, they will be unable to divulge the secret location.
Elminster Aumar of the Forgotten Realms. At the start of his book series a magelord on a dragon burns down his home village to assassinate his father, a prince of Athalantar who had abdicated. About a century later, an orc horde destroyed the entire kingdom. The present day city of Secomber is built on its capital's ruins.
The odds of a member of the Imperial Guard of Warhammer 40000 making it to retirement age are pretty low, considering that the Imperium is almost continuously at war with some if not all of its neighbors. Those that make it are generally discharged on the planet they happen to be on when they retire, and their retirement package does not include a ticket back to their home planet (which could be over a thousand light years away, depending on what events happened during their deployment). As such, there is a very good chance that anyone who enlists in a Guard regiment will never return to their home planet, let alone their home town, ever again.
Indeed, the lucky ones instead get a commission and land on the planet of the world they conquered latest, and become essentially landed gentry in that world.
Parodied in MegaTokyo, where Piro and Largo end up in Japan without any money to buy a ticket back home. They get several opportunities to fix this, yet for whatever reason, they never actually go back home.
MegaTokyo is an interesting case indeed... With the plot and Character Development going the way it is, it seems that Piro and Largo feel too tied up in the personal lives of all the people they've interacted with. As such, even if they were offered a fool-proof method to return to America, neither would likely take it.
One scene with Meimi and Junpei implies that they may end up being forced out of Japan at some point. Until then...
In The Order of the Stick, it is foretold that Durkon will return to his homeland—posthumously. However, he's actually happy to learn this because he'd much rather be buried with his ancestors than to die somewhere else.
Of course, he doesn't know the real reason he was sent away from his home in the first place: it's prophecized that when he returns, it will result in the land's destruction.
Then there's Vaarsuvius, whose quest for power cost V's marriage and nearly the lives of spouse and children.
A minor plot point in Homestuck and partially a source of angst in the first parts of the story. The kids get over it fairly quickly though. The reason they can't go home is because Earth is a desolate wasteland and they're the sole survivors of mankind.
Zeetha from Girl Genius doesn't know where her tribe is from. Everyone who was involved in her journey to Europa ended up dead one way or another.
Atop The Fourth Wall: The Gunslinger's pocketwatch was made specifically to avert this trope. Under normal circumstances, travelling to another dimension would either be fatal to him, or it would cause the dimension to assimilate him, thereby making his own dimension fatal to him. The pocketwatch prevents these effects from occurring. But then Linkara destroyed the pocketwatch, causing The Gunslinger to be trapped in Linkara's world forever, unable to return. When Linkara realizes this, he swears that he'll find a way to fix it.
The Dimensional Guardians trapped in Creturia in the web fiction serial Dimension Heroes.
In the Whateley Universe, Phase can't go home again. His family are the largest anti-mutant force on the planet.
Ultra-Man, from the Global Guardians PBEM Universe, can't go home again because his home was seventy years in the past. His parents, his siblings, and all but one of his friends are now dead, and the surviving friend is almost ninety years old and has Alzheimer's. The town he grew up in has ten times as many people in it now than it did then, and looks nothing like it did. And of course, his house is long since been bulldozed down and replaced by a shopping mall.
qntm's "Be Here Now" story introduces a multiple-universes system of time travel. It's impossible to time-travel in one's own timeline, but you can "jump the tracks" to any point in any other timeline. The only thing is, the destination timeline is always "the next one down the [infinite] chain", so you can never go back home again once you've time-jumped once.
Survival of the Fittest: At the end of v3, JR Rizzolo manages to return home after (ostensibly) being the Sole Survivor, only to find that his family has disowned him and completely moved out.