Destination: Neptune shows an optimistic vision of commercial space exploration in the next century. Players control an organization with the resources and intent to explore, develop, and colonize the worlds beyond Earth. Organizations that practice careful planning and resource management, with a healthy dose of technology research will succeed. Destination: Neptune moves through four generations of space exploration. Players earn Victory Points by building large commercial outposts and colonies, as well as from fame and outright purchases. After four generations, the player with the most Victory Points wins the game.

This is a card driven game in which most Cards have an action that happens immediately, and another action for all of the players (including the player who played the card). Players can also sell cards in exchange for currency. When you sell a card, it goes to an Opportunity Track and is placed to the side of the board. If the Opportunity Track already has as many cards as players, the rightmost card is discarded. You may not change the order of the cards in the Opportunity Track. Players can play cards from the Opportunity Track as if they were in their hands.

Players must use the cards to gain currency and fuel in order to launch space missions to establish bases, factories and colonies on various locations within our solar system. Careful hand and resource management is key to winning the game. In addition, players also need to research certain technologies in order to build on most locations. Technologies are researched through card play and paying currency. The cards are separated into 4 piles which are separate generations. At the end of each generation, each player scores points for the various structures they've built. The game ends when all generation piles have been exhausted.