Comix Zone is a huge success, being sold out on its first day, and Alissa joins the army, eventually becoming Chief of Security for the United States. If the player defeats Mortus and the Kreeps he summons quickly enough to drain the liquid and save Alissa, an ending occurs where Alissa comes to the real world with Sketch. At the end of the game, Alissa attempts to defuse a nuke, when Mortus comes into the comic and throws her into the chamber, which starts to fill up with liquid.

It is up to Sketch to stop Mortus' evil plans and find a way out of this comic world. Ignoring Sketch's protests, Alissa sends him on his mission, keeping in touch with instructions and hints via radio. Inside the comic book, Sketch meets General Alissa Cyan, who believes he is 'the chosen one' who came to save their post-apocalyptic world from the evil of Mortus and the alien invaders. Because he does not possess any power in reality, Mortus sends Sketch into the world of his own comic, freely drawing in enemies attempting to kill him. In this instant, the main villain of Comix Zone - a powerful mutant named Mortus - manages to escape the comic book's pages, desiring to kill Sketch so he can become flesh and blood and take over the real world. One night, while Sketch is working on Comix Zone during a thunderstorm, a lightning bolt strikes a panel of his comic. Sketch Turner, a 'starving artist' and freelance rock musician living in New York City, is working on his newest comic book, named the 'Comix Zone.' Comix Zone is the story of the New World Empire's attempt to defend Earth from an invasion of alien renegades, with inspiration coming from Sketch's (oddly vivid) dreams and nightmares.

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