Flint Lockwood thinks he's a genius. But none of the things he invented are things that make sense or are useful. However, he has the support of his mother but when she dies, he's left alone with his father who thinks he should give it up. When the community that he lives in is in an economic crisis because their primary source of income, a sardine cannery, was shut down, Flint decides to try his latest invention, a machine that can turn water into food. But something goes wrong and the machine ends up in the atmosphere. Later it starts raining food. The shifty mayor tries to use this as a way to help their community, but when Flint senses something wrong with the machine, the mayor convinces him to ignore it. However, as Flint predicts, chaos ensues.

After the disastrous food storm in the first film, Flint and his friends are forced to leave the town. Flint accepts the invitation from his idol Chester V to join The Live Corp Company, which has been tasked to clean the island, and where the best inventors in the world create technologies for the betterment of mankind. When Flint discovers that his machine still operates and now creates mutant food beasts like living pickles, hungry tacodiles, shrimpanzees and apple pie-thons, he and his friends must return to save the world.