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This walkthrough is mainly concerned with the 26 singleplayer missions contained in the campaign; however, other elements of the campaign, such as researching technology, buying upgrades, interacting with characters, and exploring the Hyperion's areas and crew will also be covered.

The missions are organized in nonlinear order. There are seven subplots within the game, and each subplot contains three to five missions that must be played in order. However, players do not have to stick to one arc and play it all the way through at once; the Mission Select screen will show all missions that are available at the moment.

As exceptions to this, the Mar Sara and Final subplots make up the first and last arcs, respectively, and players cannot select any other missions while playing these. Also, some missions require that the player complete a certain number of missions before playing them: for example, Artifact Mission 2: The Dig will not appear in the menu until the player has completed a total of 8 missions.

There are three points in the campaign (Colonist 3, Covert 3, and Final 2) where you will be offered a choice to pick between two missions. You can always go back and play the mission that you didn't choose from the Mission Archives; however, note that any research, rewards, units, or storyline changes that are associated with missions you omit become permanently unavailable, and will not be unlocked even if you beat them later.