Snake hunter Dusty Crum and his team are on the hunt for invasive Burmese pythons infesting the Florida Everglades. This dangerous snake is throwing the delicate ecosystem out of balance and destroying wildlife. Dusty and his team try to catch as many snakes as possible before breeding season makes the problem worse.
When rival hunters encroach on their territory, Dusty Crum and his team risk a night raid in the dangerous Sawgrass Plains. Back at base camp, Dusty explains the process of preserving snake skins for use in clothing and boots while master tracker Gary and his daughter capture a wild hog.
Snake hunter Dusty Crum and his team set up an outpost deep in the swamp where there's less competition from other hunters but more danger from alligators and panthers. When their boat breaks down, the team mounts a critical hunt from a swamp buggy.
Dusty Crum and his team explore an abandoned missile factory that could hold the biggest concentration of pythons in the Everglades. With the snake breeding season near its end, pressure mounts to catch the reptiles before they can lay eggs.
Hunter Dusty Crum is tracking snakes through a dense pine forest when he catches a python with unusual markings. He sends a sample to a geneticist who says he has caught a new hybrid species. This hybrid can survive in colder temperatures, increasing its range and putting more wildlife in danger.
When a potentially record-breaking python escapes Dusty's grasp, his obsession to catch it brings him face to face with the massive reptile in the most dangerous solo mission of his career.