Work-related musculoskeletal disorders (MSDs) are among the leading causes of work-related disability, traditionally attributed to physical and ergonomic factors, though psychosocial and demographic factors also play a crucial role in their progression. This systematic review aimed to evaluate how these three domains are jointly analyzed and modeled in research on work-related MSDs. Scopus, Web of Science, PubMed, and Taylor & Francis were searched for publications from 2000 through 2025, selecting 655 articles for general analysis and 36 for the systematic review; methodological quality was assessed using Joanna Briggs Institute (JBI) checklists, and results were synthesized narratively. The lower back and neck were the body regions most affected across sectors. Job insecurity (risk factor) and job control/autonomy (protective) were the psychosocial factors most consistently associated with MSD outcomes, while workload alone was not significant when tested independently. Repetitive movements and forced postures predominated among ergonomic factors. Age and sex modified these associations consistently, whereas BMI showed a mixed direction, indicating context-dependent susceptibility rather than universal risk. A seven-category taxonomy was developed to classify the statistical relationships tested between domains; only five of the 36 studies formally tested statistical interaction (four across domains), with mixed results, while most reported independent or independent adjusted associations. This gap between the field’s theoretical assumption of synergy across domains and the limited empirical testing of it underscores the need for multidimensional assessment. The evidence is limited by predominantly cross-sectional designs; future research should prioritize longitudinal designs and formal interaction testing.