The player progresses through levels in Splice by rearranging groups of cells into target structures. The player has a limited number of moves (or "splices") to create each target structure; finishing a level in the fewest number of moves possible unlocks an "Angelic" achievement result. Over the game's seventy-seven levels, the player will encounter power-up cells with special abilities (for instance, cells that destroy themselves and their children). The player must learn to use these increasingly complex cells to form increasingly complex target structures.
Splice's soundtrack was composed and recorded in-house by Cipher Prime co-founder Dain Saint. The soundtrack containing the music used in the first seven sequences of the game, Flight of Angels, and the soundtrack containing the music used in its epilogue, Algorithms and Angelology, are both available for download on Cipher Prime's website.