Gene therapy alters the genome by introducing the engineered genetic material into the target cells. Gene addition and gene editing are the types of gene therapy. There are two major avenues in planning gene therapy. One is direct delivery of genetic material in vivo using viral or non-viral vectors; other is to create desired cells in vitro later to be scaffolded into the host. The broader aim of regenerative medicine is to rejuvenate or replace tissues impaired by trauma, degeneration, or other disease processes. There are several challenges with regenerative therapy, including targeted delivery of biomolecules, bioavailability of delivered molecules, and disturbed healing pathways. Combining gene therapy with regenerative medicine would increase the scope of this combination therapy in treating a variety of genetic, degenerative, and traumatic pathologies with synergistic benefits. This combined therapeutic approach has been tried in several musculoskeletal conditions, such as cartilage injuries and degeneration, meniscal tears, disc degeneration, muscle, tendon, and ligament injuries. Preclinical reports are promising. However, clinical studies are limited to certain conditions. There are some gaps to be addressed, which include best candidate gene or best combination of genes to be transduced, ideal vectors, and most adapted cell source for transfer. Requirements for medical regulatory boards should be considered to adapt the combined regenerative and gene therapy solutions into clinical practice.