Plot

Set in March 1975, a few months after the events of Peace Walker, Snake infiltrates an American black site on Cuban soil called Camp Omega to extract two prisoners.

Set in March 1975, a few months after the events of Peace Walker, players control returning protagonist Snake, also known as Big Boss, as he works with Militaires Sans Frontières (commonly abbreviated as MSF) to infiltrate an American black site on Cuban soil called Camp Omega. Once used as a refugee camp for people fleeing Cuba and Haiti, Camp Omega is home to an old prison that is being used for extraordinary rendition as it has no legal recognition under the United States Constitution. Snake's main objectives are the extraction of Paz Ortega Andrade, who has information regarding the whereabouts of the person or persons known as Cipher; and Ricardo "Chico" Valenciano Libre, a Sandinista and former child soldier who was captured by Skull Face, the commander of paramilitary force XOF, who are in control of Camp Omega. Snake's mission is supported by Kazuhira "Kaz" Miller and Huey from MSF's Mother Base in the Caribbean Sea.—Detective Ham

In the aftermath of the Peace Walker incident, Paz Ortega Andrade is missing and presumed to be dead. Under the direction of Kazuhira Miller and Huey, Militaires Sans Frontières turn their attention to an upcoming inspection by the UN amid suspicions that they possess a nuclear weapon, which MSF believe to be an attempt by the Cipher organization to stifle them. Their preparations are interrupted when MSF agents in Cuba investigate reports that Paz survived and has been detained at Camp Omega. The situation is complicated when Ricardo "Chico" Valenciano Libre attempts to rescue her and is similarly captured. Believing that both of them could compromise MSF, Snake is sent to infiltrate Camp Omega and extract them if they are alive, or confirm that they are dead and if so, determine what they revealed to their captors. Snake also recognizes the value in rescuing Paz, as he believes doing so will convince Cipher to stand down while Paz will be more willing to discuss Cipher's activities with MSF.

Snake infiltrates Camp Omega as a mysterious Special Forces unit known as XOF departs. He locates and extracts Chico, who claims Paz is dead. Using a recording that Chico gives him, Snake and Miller deduce that Paz is alive, and was moved deeper into the camp. He sneaks into Camp Omega and manages to rescue Paz as well, with the group escaping via an MSF helicopter designated Morpho One. However, on the way back to Mother Base, Chico discovers that Paz was surgically implanted with a bomb, prompting Snake and an MSF medic to remove it by hand. They then arrive to Mother Base to see it in flames as XOF forces attack. Morpho One lands long enough for Snake to rescue Miller, who claims that the UN inspection was nothing but a ruse for the XOF ambush, which razes Mother Base. As they attempt to escape XOF, Paz regains consciousness and warns everybody that there is a second bomb inside her body. Knowing that she is about to die, she jumps out, trying to throw herself clear of the helicopter. She succeeds, but the explosion causes Morpho to spiral out of control and collide with a pursuing XOF helicopter.

The epilogue reveals that the United States government downplayed MSF's destruction and attempted to cover up their dealings with the organization, as do many of MSF's clients. There are no known survivors of the assault, apart from Snake and Miller.

In a post-credits scene, set prior to Snake's arrival at Camp Omega, Paz is being interrogated by Skull Face, who demands the whereabouts of Cipher / Zero, as Paz had met Zero in person. Paz eventually gives in and agrees to tell him Zero's location before the scene ends.