Exoskeleton devices are designed for applications such as rehabilitation, assistance, and haptics. Due to the nature of physical human–machine interaction, designing and operating these devices is quite challenging. Optimization methods lessen the severity of these challenges and help designers develop the device they need. In this paper, we present an extensive and systematic literature search on the optimization methods used for the mechanical design of exoskeletons. We completed the search in the IEEE, ACM, and MDPI databases between 2017 and 2023 using the keywords “exoskeleton”, “design”, and “optimization”. We categorized our findings in terms of which limb (i.e., hand, wrist, arm, or leg) and application (assistive, rehabilitation, or haptic) the exoskeleton was designed for, the optimization metrics (force transmission, workspace, size, and adjustability/calibration), and the optimization method (categorized as evolutionary computation or non-evolutionary computation methods). We discuss our observations with respect to how the optimization methods have been implemented based on our findings. We conclude our paper with suggestions for future research.