H.E.A.T. are called to help the Central America Republic of Costo Rojo deal with "El Gusano Gigante", a mutated worm that is devouring untold amounts of crops. The country's ruler, General Albondiga, uses an experimental bio-weapon against the worm and Godzilla, but the worm is only strengthened by the attack. Mendel must synthesise an antidote for the poisoned Godzilla, then find a way to defeat El Gusano without Albondiga interfering.

In response to a sanitation workers' strike, a colony of petroleum-eating microbes, controlled by nanotechnology, are released to try to curb New York's garbage problem. Unfortunately, the microbes quickly grow out of control and now the team and Godzilla must find a way to stop the colony before it devours Manhattan.