In MySims Agents, the player must stop the evil plans of Morcubus. To accomplish this, the player must recruit different MySims with different traits to do different things to make a crime-busting team. You do many tasks such as following footprints, picking locks, hacking computers, and collecting clues and evidence to the case. The player has many gadgets to use to help with these tasks. There are many locations that you must look for clues and evidence, including an icy cave with a yeti, a spooky mansion, a beach boardwalk, and even an ancient temple. The game relies heavily on the Wii motion control for doing tasks. You also have your own headquarters, for which you can customize the layout and put down furniture unlocked during the mysteries.
As the game progresses, one of the characters, Dr F, tells the player "it's dangerous to go alone, take this" before giving them an item. This is in reference to the famous quote from the old man in the first Legend of Zelda game.