The story finds Tyson Rios and Elliot Salem as self-employed private contractors, who, along with Alice Murray run Trans World Operations (TWO), hence the game's title. Their second mission as the newly formed company takes them to Shanghai where they are tasked with meeting a contact named JB. Upon meeting him it is revealed that he was once an SSC Operative who also worked for Dalton. JB leads them to a back alley where their gear and equipment have been stashed in a dumpster. They then proceed with the second part of their mission in the form of planting locator beacons throughout strategic locations in Shanghai. After planting the last of the beacons and an encounter with overzealous security guards, they regroup on a rooftop of a building.
When Alice radios in, telling them they will get extra cash for terminating JB, a Morality Moment comes for the first time, and the players can decide to either kill him or spare him by lying and telling Alice that he escaped. Following the sequence in which JB's fate is decided, a cut scene triggers showing Shanghai under attack as the city is mostly destroyed by a terrorist attack. Rios and Salem barely escape the rooftop and ascend the building, encountering groups of mercenaries that have specifically targeted them. They manage to contact Alice who informs them that she is alive, but is trapped in the South African Consulate. They set course for the consulate, dispatching waves of mercenaries through toppled and burning buildings as well as encountering civilian hostages, which the players can choose to leave to die or rescue. Rios and Salem discover Alice being held hostage in an office. After freeing her, the three fight their way to the main hall of the consulate where a cutscene triggers a helicopter crashing through the building and subsequently creating a hole on the floor for them to escape.
- is a system that allows two players to tactically control the target of their enemy's attacks and possibly change the outcome
- In The 40th Day players are forced to make moral decisions that affect the story of the game. At pre-determined points in the game, players will be presented with a choice
- Aggro is measured by a element that displays which player the enemy characters are currently focusing on
- While one player has aggro, the other is usually being ignored and as a result, can then freely perform actions such as flanking or sniping. In The 40th Day, additional non-aggressive actions can affect aggro. For example, by performing a mock surrender the enemy combatants will focus all of their attention on the player that is surrendering, allowing the other to perform a surprise attack. Some non-aggressive acts can be performed cooperatively as well