Abstract Regenerative medicine encompasses emerging biologic interventions including platelet-rich plasma (PRP), mesenchymal stem cell (MSC) therapies, and tissue engineering approaches that harness growth factors and cellular biology for musculoskeletal repair. While individually effective, recent evidence demonstrates that combining regenerative therapies with evidence-based physiotherapy protocols produces superior functional outcomes, sustained pain relief, and structural tissue regeneration compared to monotherapy approaches. This evidence-based review examines the synergistic mechanisms, clinical efficacy data, and integrated rehabilitation frameworks that optimize outcomes in orthopedic tissue disorders. A comprehensive scoping review of recent clinical trials and meta-analyses reveals that combined regenerative medicine with progressive exercise therapy significantly improves pain, function, and quality of life in knee osteoarthritis, rotator cuff pathology, tendon injuries, and cartilage defects. Critical gaps persist regarding standardized treatment protocols, long-term cost-effectiveness, optimal timing of physiotherapy initiation, and biomarkers predicting individual responder status. This review provides clinically relevant evidence supporting the integration of physiotherapy with biologic interventions, emphasizes mechanisms of synergy between growth factor delivery and mechanical loading, and highlights future research priorities essential for advancing precision medicine approaches in orthopedic rehabilitation.