Trauma Center: Second Opinion follows the story of Dr. Derek Stiles, a newly qualified surgeon at Hope Hospital in 2018. After completing his residency, he is faced with a series of routine surgeries to get settled into his new role. However, it soon becomes apparent that Dr. Stiles has a rare ability known as the "healing touch", which allows him to slow down time during surgery, increasing accuracy and speed. This newfound skill is put to the test as a deadly disease begins to spread.
Trauma Center: Second Opinion builds upon the gameplay of its predecessor, Trauma Center: Under the Knife , which was originally released for the Nintendo DS. The Wii version features updated controls utilizing the Wii remote and Nunchuk, along with new missions and additions. In each mission, players take on a 1st-person point of view as Dr. Stiles, completing surgeries within a time limit while avoiding mistakes. A variety of tools are at their disposal, including scalpels, forceps, and surgical lasers, which can be selected using the Nunchuk. The Wii remote is used to perform actions with these tools during surgery. Assistance from the player's assistant helps complete each procedure, and ratings are given after each mission based on completion time and accuracy.