In 1984, nine years after the events of Ground Zeroes, legendary soldier Big Boss awakens from a coma in a hospital in Cyprus. He narrowly survives an assassination attempt and escapes with the help of a mysterious man named Ishmael and a bandaged patient (later revealed to be a decoy).

Now calling himself Venom Snake, Big Boss forms a new private military company called Diamond Dogs, operating out of an offshore base. His goal: to rebuild and exact revenge on those who destroyed his former group, Militaires Sans Frontières.

As Snake leads missions across Afghanistan and Central Africa, he confronts enemies like the rogue XOF unit led by Skull Face, who plans to use a terrifying bioweapon to control language and thought. Snake also encounters bizarre enemies like the silent sniper Quiet, the monstrous Man on Fire, and the telekinetic child Tretij Rebenok.

Throughout his journey, Snake uncovers the horrifying truth: he is not the real Big Boss, but a body double created to protect the real one’s identity. The man once known as a legend has passed his legacy onto a phantom — Venom Snake.

The game ends with Venom Snake accepting his role, while the true Big Boss disappears into the shadows, preparing for a greater plan that will shape the future.