Told in a documentary style, the H.E.A.T team are called to Miami to deal with Skeetera, a giant mutated female mosquito, when they come under attack from S.C.A.L.E. (Servants of Creatures Arriving Late to Earth), an eco-terrorist group - led by Alexandra Springer (voiced by Linda Blair) - who believe mutations are the next stage of evolution. After narrowly capturing the rampaging insect, H.E.A.T transport Skeetera to Monster Island so she can be studied by the U.S. military. But unknown to them, they have unwanted guests: Animal and Audrey have stowed away on board the 'Heat-Seeker', hoping for a good story, and S.C.A.L.E. has tracked them to Monster Island. When the terrorists take over Monster Island with plans to release the monsters held there, the only hope lies in the combined forces of H.E.A.T, Major Hicks and his troops, Audrey and Animal.

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.