Lillian Murphy and Ethan Hoyland are two medical interns under the supervision of the experienced Dr. Paul Wise, a physician known for his insightful knowledge of medicine practice and lack of social grace. They are sent by him to emergency locations to investigate and find clues about a patient's disease.
Dr. Wise: Medical Mysteries is a hidden object game using the conventions of medical TV shows as the main theme. As either Lillian or Ethan, the player has to search and find all the evidence items listed at the right side of the screen, on the locations related to the case and victim of some condition. Entries written in certain colors can only be collected using one of the four special gadgets at the bottom-right corner.
The sampler syringe extracts any liquid substance, the toxicity detector turns the whole scene green, making contaminated objects glow for a few seconds, the flashlight reveals items hidden in the dark and the magnifying glass replaces the cursor, enlarging a rectangular section of the screen to make the search for small objects easier. The hint button shows the position of one of the required items, but takes some time to recharge after use. A mini-game appears between levels, where hexagonal tiles have to be laid on a board to find the correct sequence of evidence, solving the case by trial-and-error.