Fifteen years after a mysterious and catastrophic event at the Janjira nuclear power plant in Japan, which resulted in the death of his wife, scientist Joe Brody becomes obsessed with uncovering the truth behind the incident. Convinced that the official explanation of seismic activity was a cover-up for something more ominous, Joe convinces his estranged son, Ford, a U.S. Navy bomb disposal officer, to accompany him to the quarantined zone in search of answers. They discover that the disaster was caused by a giant creature, and their investigation leads to the revelation of a classified project to study and contain ancient, massive creatures known as "MUTOs."

Meanwhile, the emergence of another titanic entity, long thought to be a myth, stirs from the depths of the ocean. The existence of this colossal creature, which seems to challenge and balance the newly arisen threats, forces humanity to reevaluate its understanding of nature's hierarchy. As the MUTOs wreak havoc, causing untold destruction, it becomes clear that traditional military might is ineffective against such formidable opponents. The world finds itself helpless in the wake of these prehistoric forces, leading to a desperate and uncertain gambit with the hope that the mythical giant might be the key to their survival.