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The developments to be used are determined during setup, allowing players to make strategic plans based on them before play begins. One group of eight developments is always in play. The game includes a suggested set of sixteen additional developments for your first game; in later games, players randomly select which side of eight double-sided "small" developments and eight double-sided "large" 9-cost developments to use during setup.

Many worlds that players can acquire have special powers, with these worlds being drawn from a bag during the Explore phase. Unlike in Race, in New Frontiers worlds need colonists to be settled, in addition to either payments or conquest.

Some worlds are "windfall" worlds and receive a good upon being settled. Others are production worlds and receive goods when the Produce action is selected. Goods can be traded for credits or consumed for victory points.

Play continues until one or more of four game ending conditions is reached. After all actions for that round have been done, the player with the most victory points from settled worlds, developments, 9-cost development bonuses, and VP chips earned from consuming goods wins.