Healthcare organizations face emerging challenges that threaten the safety of professionals and patients, as well as the performance and long-term sustainability of healthcare systems. Health problems such as work-related musculoskeletal disorders (WRMSD) are highly prevalent among nurses, not only due to the physical demands but also because of significant psychosocial stressors and mental health challenges inherent in healthcare environments. This study investigates the impact of psychosocial risks at work on the occurrence of WRMSD in nurses. A cross-sectional study was conducted, using a snowball recruitment method, from Octobre 2025 to March 2026, among 266 nurses. Data were collected using the Psychosocial Risk Factors scale (INSAT_ERPS) and The Depression, Anxiety and Stress Scale - 21 Items (DASS-21), and analyzed with descriptive and inferential statistics to analyze the predictive role of the psychosocial risk on burnout dimensions. This study analyzed the relationships between PSR, mental health and WRMSD. Key psychosocial determinants of WRMSDs include high psychological strain—manifesting as anxiety—compounded by psychosocial stressors such as low job control, role ambiguity, and barriers to professional development. The results highlight the importance of addressing PSR and mental health, to reduce the incidence of WRMSD among nurses. Interventions focused on improving working conditions and promoting mental health may be effective in preventing WRMSD.