As the movie opens, Rambo is still living in Thailand, having traded underground stick fights for underground snake handling. He rents out his boat, helps the local handlers catch snakes and does various other odd jobs, living a seemingly quiet life. But that changes when a group of Christian missionaries from Colorado hire him to take them into Burma, where they want to bring medicine and food (and Jesus) to the persecuted Karen people. Stallone (who directed in addition to once again co-writing the screenplay) opens the movie with real-life footage of atrocities in Burma, setting the stage for movie's cheap exploitation, reducing the people of Burma (on both sides of the conflict) to faceless cannon fodder.
Like Afghanistan in Rambo III, Burma is just a convenient place for Rambo to go kill a bunch of people without feeling conflicted about what side he's on, so it's especially disingenuous for Stallone to pretend like he's doing some sort of humanitarian good deed by highlighting the paramilitary campaign against the Karen minority. The violence in this movie makes the second and third films look like G-rated Disney movies, and Stallone doesn't just rack up the body count; he also makes every kill as graphic and gory as something out of a Saw or Hostel movie, with limbs getting hacked off, heads exploding and blood and guts flying everywhere. At least the second movie humanized Rambo's Vietnamese love interest and the third movie had him bond with an Afghan kid. The Burmese characters in this movie (including the sadistic villain, played by Maung Maung Khin) have no personalities, and what little dialogue they get is often presented without subtitles, as if to further underline how unimportant they are.
The American missionaries aren't much more fully developed, and the connection between Rambo and compassionate missionary Sarah (Julie Benz) is little more than a plot device to get him in place to slaughter Burmese soldiers. Presumably Rambo's reputation has brought numerous people to him over the past two decades seeking help, so why after all this time is this the one plea he agrees to? There's no personal connection (Richard Crenna died in 2003, so Col. Trautman doesn't show up), and the missionaries' pitch is pretty weak. But Rambo helps them get into the country and then returns to save them when they inevitably get captured, leading a team of generic mercenaries that feel like the sketchy first draft of The Expendables.
As a character, Rambo is a bit more like the haunted, traumatized veteran of the first movie than the gung-ho warrior of the second and third, but that just makes his murder spree feel like drudgery, the resigned obligation of a man who's no longer fighting against the killing machine that the military turned him into. A single question from Sarah about life at home propels Rambo to the perfunctory epilogue, arriving back at the ranch apparently owned by his never-previously-mentioned father. But this movie is less a culmination of a pop-culture fixture's character arc than a tired, cynical exercise in brand extension.