The hunters return to the Florida Everglades to find a new generation of pythons more formidable than ever. With the enemy multiplying, the teams add firepower--and call upon local legends for reinforcements. Zak and Aaron team up with a gladesman promising to bring them to a python jackpot; Troy gets his old partner Pickle back into fighting shape; and Bruce and Kaylyn return to a monster's den. 

The teams unite to storm a hostile site that's rumored to be swarming with pythons. Attacking by land, water and air, the teams deploy buggies, boats and drones to target and eliminate a growing threat to the Everglades.