Inventor Flint Lockwood, who previously created a machine that turns water into food, returns to his hometown of Swallow Falls after his invention went haywire and caused a food storm. Flint now works for The Live Corp Company under his idol, Chester V, who tasks him with cleaning up the island. Upon arrival, Flint reunites with his friends, Sam Sparks, Manny, Brent, Earl, and Steve the monkey. They find that the food has evolved into sentient food-animal hybrids, or "foodimals," which have taken over the island. With danger lurking, Flint's team embarks on a new adventure to tackle the bizarre and potentially hazardous food creatures.

As they venture deeper into the island, they encounter various quirky and imaginative foodimals, each presenting its own set of challenges. Flint learns that his machine is still operational and now creating these foodimals non-stop. Chester V reveals ulterior motives, aiming to harness Flint’s invention for his own gain. Throughout their journey, Flint and his companions must use their wits and teamwork to navigate through a landscape filled with giant food creatures while Flint grapples with self-doubt and the realization of what true innovation and responsibility mean. The mix of action, humor, and heart propels their adventure forward toward a resolution that underscores the importance of friendship and accepting one's own strengths and weaknesses.