Introduction Degenerative disorders pose significant challenges to global health, with modern medicine striving to understand their intricate pathophysiology and develop sustainable treatments. Degenerative disorders, characterized by the progressive deterioration of bodily functions, pose significant challenges in modern medicine. Ayurveda, with its timeless principles rooted in Shareera (body constitution), provides a unique perspective. Rajayakshma, a condition characterized by systemic degeneration, offers an archetype for studying degenerative disorders through the lens of Ayurveda. Recent research bridges traditional concepts with modern medical insights, providing a comprehensive understanding of such disorders. Methods: A systematic review of classical Ayurvedic texts, including Charaka Samhita, Sushruta Samhita, and Ashtanga Hridaya, is conducted to extract the principles of Rajayakshma. Recent advancements in molecular biology, systems biology, and bioinformatics were examined to integrate modern scientific findings with traditional Ayurvedic knowledge. Clinical trials and case studies focusing on Ayurvedic interventions for Rajayakshama were also analyzed to assess their efficacy and therapeutic potential Results: The Ayurvedic concept of Dhatukshaya (tissue depletion) in Rajayakshma aligns with the progressive degeneration observed in modern degenerative disorders. Innovations in understanding the Agni (digestive and metabolic fire), Tridosha imbalances, and the role of Ojas (vital essence) have provided new insights into disease mechanisms. Molecular studies demonstrate parallels between Ojas depletion and oxidative stress-induced cellular damage. Advances in diagnostic approaches, such as pulse analysis and prakriti-genomics, offer tools for early detection of degenerative processes. Therapeutic interventions focusing on Rasayana (rejuvenation therapy) have shown promise in clinical trials, improving quality of life and mitigating progression. Dravya like Ashwagandha and Shatavari, alongside Panchakarma therapies, exhibit potential for tissue regeneration and restoration of homeostasis. Discussion: The integrative approach of Ayurveda enriches the understanding of degenerative disorders through a holistic framework. The principle of Samprapti (pathogenesis) highlights multifactorial etiologies, including lifestyle, environmental, and genetic factors, providing parallels to epigenetic theories in modern medicine. Innovations such as the application of nanotechnology in Ayurveda (Bhasma preparations) and evidence-based validation of traditional therapies underscore the relevance of Shareera in contemporary healthcare. Conclusion: Ayurveda's principles of Shareera provide a profound foundation for understanding and managing degenerative disorders. The study of Rajayakshma exemplifies how traditional knowledge can synergize with modern innovations to offer integrative, patient-centric approaches. Further interdisciplinary research and clinical validation are essential to enhance its applicability in global healthcare systems