A mysterious female assassin attacks the X-Mansion, knocking out the X-Men one by one. Wolverine finds out that the assassin is his clone, designation "X-23", created by the Dr. Deborah Risman and raised without love to be a living weapon.
Rogue falls under the mind control of Mesmero and is used as a weapon to absorb the mutant abilities of every X-Man, Brotherhood, and Acolyte member. Mesmero wants Rogue to give all of her stolen abilities to Apocalypse to awaken him.
The X-Men, Brotherhood, and Acolytes continue their battle against Mesmero. The heroes and villains track down Apocalypse to Egypt, but only to come face-to-face with him and having failed to prevent Apocalypse from coming back to life.
Taking a break from superhero duty, the X-Men take a pleasure cruise. However, Magma becomes violently ill, literally suffering from earth withdrawal. When Boom Boom and Iceman take her to an island, she accidentally triggers a volcano.
A strange phenomena occurs in the wake of Apocalypse, and the X-Men receive permission from the government to study it. Meanwhile, Nightcrawler tries to revive his mother Mystique who is still trapped in stone, much to the dismay of Rogue.
In order to prevent all of humankind from being turned into mutants, the X-Men, the Brotherhood, S.H.I.E.L.D., The Acolytes, Angel, Spyke, Havok, and the New Mutants all join forces to save humanity from the ambitions of Apocalypse.