When a group of missionary aid workers in Myanmar disappear into the vast green inferno, vigilante Vietnam War veteran John Rambo (Sylvester Stallone) leaves his job as a Salween River boatman behind to accompany a group of mercenaries on a daring rescue mission. It's been 20 years since Rambo helped mujahedeen rebels fend off Soviet invaders in Afghanistan, and these days the former soldier lives a simple life in northern Thailand. Meanwhile, the world's longest-running civil war rages into its 60th year on the nearby Thai-Burma border. One day, human rights missionaries Sarah Miller (Julie Benz) and Michael Burnett (Paul Schulze) show up asking Rambo to guide them up the Salween so they can get some much-needed food and medical supplies to the desperate Karen tribe. According to Sarah and Michael, the Burmese military has planted land mines all along the roads leading into the tribe's village, making it virtually impossible to reach the tribe via land. Two weeks after Rambo drops the group off in dangerous territory, pastor Arthur Marsh (Ken Howard) arrives with a chilling message: the aid workers never returned from their mission into the jungle, and the embassies refuse to help Marsh and his fellow missionaries find their missing friends. Now, despite the fact that Rambo has long since sworn off all forms of violence, the knowledge that innocent missionaries are being used as pawns in a brutal war leaves him with no other choice than to venture behind enemy lines on his most dangerous mission to date.