The quality of life for patients and those caregivers can be greatly reduced by muscle disorders that results in a loss of function and mobility. For abnormalities and disorders of the muscles, there are limited therapy choices. One of the barriers to the creation of novel treatment approaches is the “blood-muscle barrier,” which refers to the slow rate at which drugs diffuse from blood vessels to muscle. Consequently, the efficient therapy of muscle disorders depends on drug delivery methods and techniques that specifically target muscles. Musculo-targeted drugs and their delivery strategies to the musculoskeletal system are comprehensively covered in this chapter. Basic information regarding the morphology and molecular biology of muscle is also described to improve our comprehension of the existing musculoskeletal targeted drug delivery systems.