In each round in Mission: Red Planet, players start by secretly deploying one of their character cards, with this card determining both when they place astronauts on the spaceships awaiting launch to Mars and which special action they take during the round. Each spaceship has a specified destination, and until an astronaut sets foot in a region, no one knows which resource they'll find. Players collect resources (worth points) three times during the game, and they each have a secret mission card that might grant them additional points at game's end. During the game, players might acquire an additional mission or a research card that changes the value of what awaits on Mars.
The 2015 edition of Mission: Red Planet features the same gameplay as the original 2005 edition, but it includes:
- Components for up to six players instead of five
- Special two-player variant rules
- New action cards and revised mission and discovery cards
- Mars' moon Phobos as a new zone that astronauts can explore before possibly returning to the planet itself