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 on a romantic cruise to Alaska, Nick and Audrey's ship is attacked by a mutated turtle, but they are saved - not by Godzilla, but by Komodithrax, a mutated Komodo dragon. When Godzilla heads for Alaska to find Nick and H.E.A.T. follow, they make a shocking discovery: Godzilla and Komodithrax are in love, and Godzilla has become surrogate father to an egg laid by Komodithrax. But with the menacing turtle still nearby, and the U.S. military ordered to destroy all monsters in the area, can Nick and the team protect the two gargantuan reptilian lovers?

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.