Chronic orthopedic pain syndromes have profound negative influences on the life’s quality, and the existing pharmacologic options provide incomplete and frequently not maintainable benefits. The research targeted to arbitrate the clinical potency of a standardized 12-week multimodal physiotherapy program involving manual therapy, structured exercise, and transcutaneous electrical nerve stimulation (TENS) in the cure of persistent musculoskeletal pain. Sixty adults experiencing orthopedic pain for at least three months were recruited and followed up at baseline, Week 6, and Week 12 with the help of validated instruments for measuring pain, function, and standard of living. These included the SF-36 Health Survey, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oswestry Disability Index (ODI), and the Visual Analog Scale (VAS). The intensity of pain reduced greatly, as VAS scores went down, from 7.1 to 2.8. There was a notable enhancement. In functional disability, with the mean ODI and WOMAC improvements of more than 18 points. There was a rise in the quality of life in most of the SF-36 domains, and 41.1% of the people reported using no analgesics at all by Week 12. The intervention was well tolerated, with minimal adverse events. These results justify the use of multimodal physiotherapy as a non-pharmacologic treatment option since it is safe, effective, and can be expanded upon. These outcomes should be confirmed, and randomized controlled trials with long-term follow-up are necessary. © 2025 Elsevier B.V., All rights reserved.