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Plague Inc.: Evolved is the follow-up to Plague Inc.. It is a strategy game, in which the player attempts to create a plague that destroys the entire world. Players can choose between a variety of plague types, including Virus, Fungus, Bacteria etc. Aside from the official types, players can also create and share custom plagues via the Steam Workshop.

Players start by initially infecting a country of their choosing. After that, the player must upgrade their plague in order to infect more people, develop different symptoms, and develop resistance to cure attempts that will gradually take place. These factors will change depending on the plague type, and the difficulty setting. The game can end for various reasons: if the plague destroys the world, if the plague is cured, or if there are survivors after all other victims have been killed.

The game offers four difficulty settings, Casual, Normal, Brutal and Mega Brutal. The game supports cooperative and competitive multiplayer modes.