Susan Murphy gets turned into a giant monster on her wedding day when a meteorite from outer space hits her. She is taken to a secret government compound where she meets a ragtag group of monsters also rounded up over the years. As a last resort, under the guidance of General W.R. Monger, on a desperate order from The President, the motley group of Monsters are called into action to combat the aliens and save the world from imminent destruction.

Radio astronomer Zane Zaminsky believes he's picked up a cosmic noise that is signaling extraterrestrial intelligence. But after turning over the tape to his boss Phil Gordian, Zane's fired, his girlfriend get transferred and his partner is found dead from an apparent suicide. Zane's desperate search for answers leads him to Mexico and a mysterious power plant this is generating more than electricity and is run by people who are not what they appear...