After the devastating events in San Francisco years earlier, the existence of titans, or massive monsters, is now public knowledge. Monarch, a secretive organization tasked with studying these creatures, faces political pressures as the world debates what to do with them. Dr. Emma Russell, a Monarch scientist, and her daughter Madison are witness to the birth of a new monster, Mothra. Emma calms Mothra using the "Orca," a device that can emit frequencies to control titans. However, eco-terrorists, led by Alan Jonah, attack the facility, kidnapping Emma and Madison, and seek to use the Orca to awaken other monsters and restore the natural order.

As titans arise around the globe, Monarch's approach pivots to a more active role under the guidance of Dr. Ishiro Serizawa and Dr. Vivienne Graham. Emma's estranged husband, Mark, a former employee of Monarch and a wildlife photographer, is recruited for his expertise with the Orca and his unique understanding of the titans. He joins the global mission to locate and stop the awakened monsters before they cause catastrophic damage. His personal stake in the mission is high, driven by the loss of his son in the San Francisco attack and the kidnapping of his ex-wife and daughter. As he navigates the internal strife within Monarch, along with the global crisis unfolding, the titans converge, signaling the beginning of an epic battle for dominance among these ancient creatures, with humanity caught in the middle.