Art of Murder 2 is a full 3-D adventure game played from a third-person perspective. Players move their character by clicking on locations shown in the main display, and each scene will only be finished when a character has completed all the actions on the screen. Players interact with NPCs as well as specific objects by clicking or dragging. An in-game hint system is located on the bottom left corner of the screen as a question mark. Items carried by players can be combined with additional items. Objects return to their original position whenever they are dropped. Interactive cut scenes are triggered once a player has completed location objectives.

To complete the game, the player explores real life locations such as Paris, New Orleans or Havana. Some game stages have a time limit that, if not completed is punishable by the character’s death. If a character dies, the player’s progress is saved automatically and the player may start over from their last save.

Art of Murder contains a range of mechanical and slider puzzles.