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Medical imaging methods have improved the detection of human diseases with increasing accuracy. The ability to probe molecular processes noninvasively or using tissue‐selective imaging agents and nanoparticles has made it possible to localize, identify the stage, and determine the functional status of pathological lesions. The challenges in detecting cancer particularly have driven the development of diverse imaging technologies. While earlier cancer imaging methods enabled preoperative evaluation, the need to track and visualize cancer location in the operating room itself has ushered in new systems capable of providing concurrent images of cancer during surgery. Intraoperative use of conventional clinical imaging modalities is often limited by bulky hardware design, prohibitive cost, lack of real‐time image display, and compatibility with conventional hardware interfaces. For these reasons, focus on fluorescence‐guided surgery (FGS) devices has increased to take advantage of real‐time, high‐resolution, functional imaging with hardware that has become increasingly amenable to miniaturization. In particular, the adaptation of wearable devices for FGS presents hands‐free capability for optimal navigation during cancer surgery. The evolution of head‐mounted devices in the operating room and adaptation for FGS is highlighted. Key challenges to wide clinical adoption of this imaging platform are identified and potential future directions are suggested. [ABSTRACT FROM AUTHOR]