In 2016, a jumbo jet carrying Senator Hach, an important politician and likely future presidential candidate, is hijacked by terrorists. In exchange for the senator, the terrorists demand from the United States government Pythagoras, a research project being conducted in the Moloni Republic in southern Africa. In an effort to identify these terrorists, the government begins an investigation of Pythagoras.

The Moloni government refuses to cooperate and work with the United States, saying that it doesn't want to interfere in its current affairs. In response, the US send in a covert special forces team to investigate, but the team is obliterated by armed resistance. With no other options and time running out, the US government calls Solid Snake to infiltrate the laboratory, discover the nature of Pythagoras, and rescue Senator Hach.