Following the success of the unmanned rover missions, the United Nations established the Department of Operations and Mars Exploration (D.O.M.E.). The first settlers arrived on Mars in the year 2037 and in the decades following establishing Mars Base Camp, private exploration companies started work on the creation of a self-sustaining colony. As chief astronaut for one of these enterprises, you want to be a pioneer in the creation of the biggest, most advanced colony on Mars by achieving both D.O.M.E. mission goals as well as your company’s private agenda.

In the beginning, you will be dependent on supplies from Earth and will need to travel often between the Mars Space Station and the planet's surface. As the colony grows over time, you will shift your activities to construct mines, power generators, water extractors, greenhouses, oxygen factories, and shelters. Your goal is to create a self-sustaining colony independent of any terrestrial organization. This will need understanding the importance of water, air, power, and food — the necessities for survival.

Do you dare participate in humankind’s biggest challenge?

On Mars is played over several rounds, each round consisting of two phases - the Colonization Phase ​and the Shuttle Phase​.

During the Colonization Phase, each player will takes a turn during which they take actions. The available actions will depend on the side of the board they are on. If you are in orbit, you may take blueprints, buy and develop technologies, and take supplies from the Warehouse. If you are on the surface of the planet, you may construct buildings with your bots, upgrade these buildings using blueprints, take scientists and new contracts, welcome new ships, and explore the planet’s surface with your rover. In the Shuttle Phase, players can travel between the colony and the Space Station in orbit.

All buildings on Mars have a dependency on each other and some are required for the colony to expand. Building shelters for Colonists to live in needs oxygen; generating oxygen requires plants; growing plants requires water; extracting water from ice requires power; generating power requires mining minerals; and mining minerals requires Colonists. Upgrading the colony’s ability to provide these resources is vital. As the colony expands, more shelters are needed so that the Colonists can survive the inhospitable conditions on Mars.

During the game, players are also trying to finish missions. Once a total of three missions have been completed, the game is over. In order to win the game, players must contribute to the development of the first colony on Mars. This is represented during the game by players obtaining Opportunity Points (OP). The player who has the most OP at the end of the game is declared the winner.