When circus master Tobias Wilson brings his 'Mutant Mania' circus to Manhattan, things go badly wrong when a mutated sea anemone, called Medusa, escapes her tank and goes on the rampage. When the team discover the creature is sucking water out of her victims, as she needs the electrolytes found in water to survive, the race is on to stop Medusa before she drinks every drop of water on the planet.

While fighting a giant mutant germ named Bacillus, Godzilla is infected by the bacteria and left fighting for his life. While Elsie, Randy and Mendel create an antibiotic to weaken the bacteria, Nick and Monique must enter Godzilla's body and destroy the infection at its source before Godzilla dies.