The game starts in Carthage, Michigan when Imani Gray and four IPCA recruits are sent in to locate Lawrence Mujari and eliminate the French Anarchiste Liberation Army (ALA) threat. Gabriel Logan and Lian Xing investigate Uganda, and Gary Stoneman investigates Italy. The IPCA agents foil the ALA's plans. Mujari has recovered and is under medical care. Meanwhile, Stone discovers that Cosa Nostra wants to retrieve the virus to use it as a tool in mafia wars. Stone goes on a mission to Pescara to assassinate the mafia head, Dimitri Alexoupolos. Dimitri's assassination prevents a Mafia family from gaining access to Syphon Filter.

The game starts in Carthage, Michigan when Imani Gray and four IPCA recruits are sent in to locate Lawrence Mujari and eliminate the French Anarchiste Liberation Army (ALA) threat. Gabriel Logan and Lian Xing investigate Uganda, and Gary Stoneman investigates Italy. The IPCA agents foil the ALA's plans. Mujari has recovered and is under medical care. Meanwhile, Stone discovers that Cosa Nostra wants to retrieve the virus to use it as a tool in mafia wars. Stone goes on a mission to Pescara to assassinate the mafia head, Dimitri Alexoupolos. Dimitri's assassination prevents a Mafia family from gaining access to Syphon Filter.