Purpose Decisions to increase work participation must be informed and timely to improve return to work (RTW). The implementation of research into clinical practice relies on sophisticated yet practical approaches such as machine learning (ML). The objective of this study is to explore the evidence of machine learning in vocational rehabilitation and discuss the strengths and areas for improvement in the field. Methods We used the PRISMA guidelines and the Arksey and O’Malley framework. We searched Ovid Medline, CINAHL, and PsycINFO; with hand-searching and use of the Web of Science for the final articles. We included studies that are peer-reviewed, published within the last 10 years to consider contemporary material, implemented a form of “machine learning” or “learning health system”, undertaken in a vocational rehabilitation setting, and has employment as a specific outcome. Results 12 studies were analyzed. The most commonly studied population was musculoskeletal injuries or health conditions. Most of the studies came from Europe and most were retrospective studies. The interventions were not always reported or specified. ML was used to identify different work-related variables that were predictive of return to work. However, ML approaches were varied and no standard or predominant ML approach was evident. Conclusions ML offers a potentially beneficial approach to identifying predictors of RTW. While ML uses a complex calculation and estimation, ML complements other elements of evidence-based practice such as the clinician’s expertise, the worker’s preference and values, and contextual factors around RTW in an efficient and timely manner.