Searching for a cure to Alzheimer's disease, a group of scientists on an isolated research facility become the prey, as a trio of intelligent sharks fight back.
Shark conservationist Misty Calhoun is invited to visit the sea-based facility Akhelios by pharmaceutical billionaire Carl Durant. She and neurobiology students Leslie and Daniel Kim are taken to the facility by Durant's associate Craig Burns on a motorboat. When they arrive, they meet Durant, as well as the facility's crew, which include shark trainers Trent Slater, Mike Shutello, and Josh Hooper, and computer technician Aaron Ellroy. As a demonstration, Durant throws Aaron into the water, letting the sharks chase him: at the last possible second, he uses a key to drive them away in formation. Durant explains that he has been genetically altering the brains of five bull sharks to make them smarter, which enrages Misty.
Dr. Emma Collins and her team are spending their third summer on the island of Little Happy studying the effect of climate change on the great white sharks who come to the nearby nursery every year to give birth. However, their peaceful life is disrupted when a "scientific" team shows up looking for three bull sharks.