When lovelorn Michael arrives in Berlin to return a set of keys to his ex-girlfriend, Gabi, as an excuse to see her again, he finds her apartment empty save for a couple of plumbers making repairs to the central heating. Just as Michael learns from the plumber’s apprentice, Harper, that Gabi has popped out for a while but will return soon, the apprentice is attacked by his boss who has unexpectedly and inexplicably transformed into a raging madman. Together, Michael and Harper manage to bundle the crazed plumber out of the apartment and barricade themselves safely inside. Within minutes, they find themselves trapped in apartment block under siege from a horde of similarly insane people, apparently hungry for human flesh.

Professor Charles Xavier and his team of genetically gifted superheroes face a rising tide of anti-mutant sentiment led by Col. William Stryker. Storm, Wolverine and Jean Grey must join their usual nemeses—Magneto and Mystique—to unhinge Stryker's scheme to exterminate all mutants.