Returning from their journey in the Mojoverse, the X-Men return to the destroyed remains of their home, the X-Mansion. They soon discover that they are in an alternate universe under the control of the evil mutant, Apocalypse. The X-Men must battle their way through Apocalypse's army of Sentinels and Mutants in order to return to their universe.
The playable X-Men roster consists of: Wolverine, Cyclops, Storm, and Rogue. Each character has a different super power that give them a unique playstyle. Boss enemies include classic villains from the comics such as Blob and Magneto. X-Men from the 616 Marvel Universe, such as Colossus and Nightcrawler are also allies of Apocalypse in this alternate universe and must be defeated.
X-Men: Reign of Apocalypse is a side-scrolling action beat 'em up with 12 distinct levels. Each level has waves of enemies plus a mutant boss who all must be defeated to progress to the next stage. Players must defeat enemies to earn points which can be spent at the end of each stage to improve the character's strength, vitality, or mutant power. Each playable character share the same basic attacks but each have a unique special ability: Wolverine has claws that excelling in close-range combat, Rogue has a charge ability, Storm controls tornado projectiles, and Cyclops has long-range optic blasts.
X-Men: Reign of Apocalypse received mixed reviews upon release. Aggregate review websites Metacritic and GameRankings scored the game 61 out of 100 and 59.34%, respectively. GameSpot recommended the portable game to X-Men and beat 'em up game fanatics, but were disappointed by the simplistic gameplay.Nintendojo concluded that it was "a fun game that ends much too quickly."