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.

Follows the heroic efforts of the crypto-zoological agency Monarch as its members face off against a battery of god-sized monsters, including the mighty Godzilla, who collides with Mothra, Rodan, and his ultimate nemesis, the three-headed King Ghidorah. When these ancient super-species, thought to be mere myths, rise again, they all vie for supremacy, leaving humanity's very existence hanging in the balance.