Background: The manufacturing sector drives global industrial growth and economic prosperity, yet concerns persist about ergonomic hazards causing widespread work-related musculoskeletal disorders (WMSDs). This study aims to examine how physical and psychological strains contribute to the risk of WMSDs among manufacturing workers in Indonesia. Method: From September 2023 to March 2024, a cross-sectional quantitative study surveyed 1714 manufacturing workers. Structured questionnaires covered demographics, work factors, psychosocial conditions, and musculoskeletal symptoms. Statistical analyses included univariate, bivariate, and multivariate methods. Result: About one-third of respondents reported high-risk WMSD symptoms over short and long terms, primarily affecting critical body regions. Males faced greater risks, while younger workers showed some protection. Physical activity levels, job factors, and psychosocial conditions significantly influenced WMSD risk. Role clarity was protective, while physical and psychological stressors increased MSD risk. Conclusion: This study highlights how physical and psychological strains jointly heighten WMSD risks in manufacturing. Targeted interventions addressing both ergonomic and psychological factors are crucial to improve workplace health and safety for manufacturing workers. Copyright © 2025 Abdul Kadir et al. Advances in Public Health published by John Wiley & Sons Ltd.