Ketika sebuah meteorit dari angkasa luar hit California gadis muda bernama Susan Murphy dan berubah ke dalam gergasi rakasa, 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 crew of Monsters is called into action to combat the aliens and save the world from imminent destruction!