(1) Background: Mixed Reality is a technology that has gained attention due to its unique capabilities for accessing and visualizing information, becoming a valuable tool for medicine, particularly for the operating room and surgical learning; (2) Methods: A systematic review was conducted following the PRISMA guidelines to answer the research questions established using the PICO framework; (3) Results: Although implementation of Mixed Reality applications in the operations room presents some challenges, when used appropriately, it can yield remarkable results. It can make learning easier, flatten the learning curve for several procedures, and facilitate various aspects of the surgical processes; (4) Conclusion: Technical complexity, equipment costs, and steep learning curves present significant obstacles to the widespread adoption of Mixed Reality and computer-assisted evaluation. The possibility of integration of distinct medical imaging modalities and innovative functionalities holds promise for clinical applications. However, it is important to consider issues related to usability, bias, and statistical analyses need consideration. Mixed Reality offers significant benefits, but there are still open challenges such as ergonomic issues, limited field of view, and battery autonomy that must be addressed to ensure widespread acceptance.