The Cortex System is based on the Sovereign Stone System. The dice used in the Cortex system are d2, d4, d6, d8, d10, and d12. Die steps are used as difficulty modifiers: a difficult action might have a two-step penalty, reducing a skill from a d8 to a d4. The next step up from a d12 in this system is an additional die, starting with d2: d12+d2, d12+d4, etc. Skills and attributes are each rated as a single die type, and both dice are rolled versus a target number.

One distinguishing feature of the Serenity RPG is the use of "plot points". Plot points are gained as rewards, and used to modify rolls, affect non-player characters (NPCs), or modify a situation for the benefit of the crew (usually for survival) or for cinematic effect. Some points also convert to advancement points (like experience points) at the end of a story or session. Advancement points are used to improve a character's skills, abilities, or attributes.

The Cortex System has become the House System for Margaret Weis Productions, Ltd.

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