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Five years after Godzilla has laid waste to San Francisco, paleo-biologist Dr. Emma Russell (Vera Farmiga) is now seperated from her husband animal behavior specialist Dr. Mark Russell (Kyle Chandler). Both worked in the development of the "Orca" a super-high-tech device overseen by a scientific-military organization called Monarch, enabling communication with many monsters recently discovered to be hibernating throughout the globe.

Emma and their 12-year-old daughter, Madison, witness the hatching of Mothra, in larva form, underneath a pyramid in China, but just as she is starting to communicate with the super-sized creature, eco-terrorist led by Alan Jonah kill all the other scientist and kidnap Emma & Madison.

The vast Monarch team enlist Mark's help in tracking Jonah, a Missing-In-Action Godzilla, and Emma and Madison before more monsters are unleashed. At a base in Antarctica, it soon becomes clear that Emma has not been kidnapped, but has joined Jonah's terrorist organization so that, together, they can destroy the world in order to save it. There, they unleash "Monster Zero", a.k.a. Ghidorah, the three-headed monster.

Soon, other monsters start attacking other great cities throughtout the world, all because, according to animal expert Mark, Ghidorah is the "alpha male" of the pack, just like wolves. And why wouldn't a 10,000 ton three-headed monster from outer space lead a pack of varied earth-born giant creatures exactly like wolves follow other wolves?