In 2008, InGen is operating a dinosaur research laboratory on Île Saint-Hubert in the Atlantic Ocean. The site is used for genetic experiments, including transgenic and mutated dinosaurs. One of these creations, a deformed six-limbed Tyrannosaur dubbed "Distortus rex", escapes containment. It kills an employee and wreaks havoc, forcing the personnel to abandon the island.

In 2025, most of Earth's climate has become inhospitable to sustain the de-extinct dinosaurs. The remaining animals survive in areas around the equator, which resemble the Mesozoic climate, making them no-travel zones.

Martin Krebs, an executive at pharmaceutical company ParkerGenix, recruits Zora Bennett, an ex-military covert operative, to collaborate with paleontologist Dr. Henry Loomis on a top-secret mission. Their goal is to retrieve biomaterial samples from the three largest remaining prehistoric specimens, which hold the key to a new heart disease treatment. In a bar in Suriname, Zora recruits her longtime friend Duncan Kincaid to lead the expedition. He brings boat driver LeClerc, mercenary Nina, and security chief Bobby Atwater.