John Rambo, a disenchanted Vietnam War veteran, leads a solitary life in northern Thailand, trapping snakes for local entertainers and ferrying locals in his old boat. Haunted by his violent past and the specter of war that never seems to leave him, he is approached by a group of Christian human rights missionaries. These idealistic workers seek Rambo’s help to guide them up the Salween River into war-torn Burma, where they intend to provide aid to the Karen people, who are suffering under the brutal rule of the sadistic Major Tint and his Burmese army.

Despite his initial reluctance and cynical view of their chances, Rambo is persuaded by Sarah, a missionary, to take them into Burma. However, soon after they arrive, Rambo's fears prove justified; the missionaries are taken hostage by Major Tint's forces. The incident propels Rambo to reverently consider a renewed sense of purpose. When a pastor associated with the missionaries hires a group of mercenaries to rescue the captives, Rambo decides to join the rescue mission. Setting aside his long-held aversion to fighting, Rambo embarks on a perilous journey into the heart of darkness, determined to confront the horrors of war once again to save the captives.