The rotator cuff is a musculotendon unit responsible for movement in the shoulder. Rotator cuff tears represent a significant number of musculoskeletal injuries in the adult population. In addition, there is a high incidence of retear rates due to various complications within the complex anatomical structure and the lack of proper healing. Current clinical strategies for rotator cuff augmentation include surgical intervention with autograft tissue grafts and beneficial impacts have been shown, but challenges still exist because of limited supply. For decades, nanomaterials have been engineered for the repair of various tissue and organ systems. This review article provides a thorough summary of the role nanomaterials, stem cells and biological agents have played in rotator cuff repair to date and offers input on next generation approaches for regenerating this tissue.