After narrowly surviving the battle with the Rathalos in the first film, Captain Artemis (Milla Jovovich) remains stranded in the world of Monster Hunter. With her new allies—the Hunter (Tony Jaa), the Admiral (Ron Perlman), and a growing team of warriors—Artemis begins to understand the deeper balance between monsters and the environment. But the peace is short-lived. Ancient forces begin to stir as the rifts between Earth and the world of Monster Hunter reopen, this time unleashing something far worse: Elder Dragons, colossal, godlike creatures capable of reshaping entire ecosystems.

The worst of these, Fatalis, an apocalyptic black dragon of legend, awakens and threatens to permanently merge the two worlds. As monsters begin to appear on Earth in greater numbers, governments prepare for war, unaware that brute force will only make things worse. Artemis and her team must travel across continents—from scorching deserts to frozen tundras—to gather rare artifacts, unite ancient enemies, and uncover the lost secrets of the Guild: an ancient order sworn to prevent world-ending threats.