Emergency doctor Natalie heads on a 3-day Everglades trip with her husband Scott and best friend Chelsea. She has a vivid nightmare: a giant python hunts her, Chelsea reveals she’s pregnant with Scott’s child, Scott abandons her in the swamp, and the serpent kills her. She wakes up on the boat right before the nightmare starts.
Small details from the dream keep coming true, proving she can see the future. Using her emergency skills, Natalie saves April and preps the cabin, but Scott and Chelsea dismiss her as crazy. When the python strikes, they beg for shelter outside.
The rescue team underestimates the python. One rescuer dies after the group misuses a sonic snake repeller, luring the snake to overturn their boat. As survivors flee to a fire tower and aid station, more people fall victim to the beast. Selfish Scott locks Natalie and April out of an SUV. Natalie sneaks the sonic device into the trunk. The python chases the sound and crashes the vehicle.
Cornered, Chelsea confesses her secret. Scott tries to sacrifice her, and she pulls him down to be eaten together. Natalie, Owen and April survive. The next morning, Natalie removes her wedding ring, leaves her toxic marriage and accepts Owen’s dinner invite, embracing her new beginning.
