The comic serves as an alternative conclusion to The 13 Ghosts of Scooby-Doo, the only elements kept from Scooby-Doo! and the Curse of the 13th Ghost being Flim-Flam having aged since the events of the original show as well as the 13th and final ghost from the Chest of Demons being Asmodeus and having the backstory of being a corrupt ancestor of Vincent Van Ghoul who turned into a demon.
The story begins with Mystery, Inc. having a barbecue at the house of Scooby's sister Ruby Doo and his nephew Scrappy-Doo, when they suddenly get a call from Vincent Van Ghoul's crystal ball that he's found the last of the 13 ghosts. Mystery, Inc. must then work together to recapture Asmodeus and put an end to the debt Shaggy and Scooby owe Vincent Van Ghoul.
- Adapted Out: Mortifer Quinch from Scooby-Doo! and the Curse of the 13th Ghost is left out, his role as a companion of Vincent Van Ghoul who originally helped him capture the 13 ghosts being split between Boris Kreepoff and Miss Grimwood.
- Big Bad: Like in Curse of the 13th Ghost, the main villain is the 13th and final ghost Asmodeus. Unlike the direct-to-video film, this Asmodeus is the real deal and not a crook in a costume.
- The Cameo:
- Scrappy looks through photos of his cherished adventures in the beginning of the story. Characters shown in images who don't play a role in the story include his friends Duke and Annie from the Scooby-Doo and Scrappy-Doo episode "The Ransom of Scooby Chief" as well as Dynomutt and the Blue Falcon.
- The Crypt Keeper as depicted in Tales from the Cryptkeeper appears on a television set Elsa Frankenteen turns on to get the attention of Zomba.
- Iddesvigg, the Ridiculously Cute Critter Vincent Van Ghoul befriended in the original series episode "When You Witch Upon a Star", can be seen in the penultimate panel of the last page.
- Canon Foreigner: Shaggy Rogers is given a nephew of his own named Orville, who is nicknamed "Taggy".
- Canon Welding: While serving as a conclusion to The 13 Ghosts of Scooby-Doo, the comic also features characters from and references to the events of A Pup Named Scooby-Doo, Scooby-Doo Meets the Boo Brothers, Scooby-Doo and the Ghoul School, Scooby-Doo! and the Reluctant Werewolf, several of the films in the Scooby-Doo Direct-to-Video Film Series (particularly Scooby-Doo on Zombie Island, Scooby-Doo! and the Witch's Ghost and Scooby-Doo and the Alien Invaders), and the video game Scooby-Doo: Mystery Mayhem.
- Connected All Along: It is established in the comic that Miss Grimwood and Vincent Van Ghoul knew each other because she was one of the people who originally helped Vincent Van Ghoul seal away the 13 ghosts.
- Continuity Nod: There's a truckload of references to past Scooby-Doo works.
- The very beginning of the story has Scrappy reminisce on past adventures, such as his friends Duke and Annie helping him rescue Shaggy and Scooby in the Scooby-Doo and Scrappy-Doo episode "The Ransom of Scooby Chief" and participating in the Monster Road Rally in Scooby-Doo! and the Reluctant Werewolf.
- Asmodeus' sole minion in the story aside from the released Zomba, Time Slime, Marcella, and Professor Phantazmo is Selena Drake, the main villain of Scooby-Doo: Mystery Mayhem.
- When talking about what he'd been through ever since the mission to recapture the 13 ghosts came to a premature halt, Shaggy mentions that he hired ghosts to clear out his dead uncle's haunted house, did teaching at a ghoul school, and participated in a monster race.
- Fred asks for Shaggy on advice for how he should explain his feelings toward Daphne, pointing out that Shaggy has experience with women and would be used to rejection due to breaking up with Googie and Crystal having to return to her home planet.
- Dhampyr: It is revealed that Sibella is half-human due to having a human mother.
- Fantastic Racism: Time Slime tries to turn the rest of the Grimwood Girls against Sibella and Elsa by revealing that Sibella has a human mother and that Elsa has a human grandfather. Winnie and Tanis are disgusted that Time Slime would think they'd have a problem with their friends having human relatives.
- Fix Fic: The whole point of the comic is to provide an alternate ending to The 13 Ghosts of Scooby-Doo for fans who weren't satisfied with the direction taken by Scooby-Doo! and the Curse of the 13th Ghost.
- HeelFace Turn: Bogel and Weerd decide to switch sides when Asmodeus rejects them. Once the gang succeed in returning Asmodeus to the chest, they decide to make amends for originally tricking Shaggy and Scooby into opening the Chest of Demons and releasing the 13 ghosts by offering to guard the Chest of Demons from anyone else who tries to open it.
- Mythology Gag: The logo for the Cadaver Land amusement park Professor Phantazmo ends up at after his release is a grinning green zombie face, similar to the logo for Spooky Island in the 2002 live-action film.
- Related in the Adaptation: In this story, Zomba is revealed to be cousins with Revolta, the main antagonist of Scooby-Doo and the Ghoul School.
- Rump Roast: Matches defeats Zomba and Revolta by breathing fire at their rear ends.
- "Scooby-Doo" Hoax: The comic begins with Mystery, Inc. having a barbecue to celebrate one of their routine cases, where a jewel thief named Nestor Crowley tried to scare away people from discovering his jewel thefts by disguising himself as the Poughkeepsie Phantom.
- Shock and Awe: Marcella tries to electrocute Scooby-Doo. Elsa Frankenteen neutralizes the attack by absorbing the lightning with her body. Being a Frankenstein monster, it doesn't harm her in the least.
- Taken for Granite: Asmodeus turns Selena Drake to stone for only succeeding in releasing four of the ghosts from the Chest of Demons.
- We Will Meet Again: Upon being returned to the Chest of Demons, Asmodeus vows that someday he and the other 12 ghosts will be freed from the chest again and that they will get even with Mystery, Inc. and friends when that happens.