When the magic powers of The Tablet of Ahkmenrah begin to die out, Larry Daley spans the globe, uniting favorite and new characters while embarking on an epic quest to save the magic before it is gone forever.

After Megamind, a highly intelligent alien supervillain, defeats his long-time nemesis Metro Man, Megamind creates a new hero to fight, but must act to save the city when his "creation" becomes an even worse villain than he was.

Animal pals Alex, Marty, Melman, and Gloria are still trying to make it back to New York's Central Park Zoo. They are forced to take a detour to Europe to find the penguins and chimps who broke the bank at a Monte Carlo casino. When French animal-control officer Capitaine Chantel DuBois picks up their scent, Alex and company are forced to hide out in a traveling circus.