Aim <p>This systematic review and meta-analysis explores the efficacy of vocational rehabilitation for people with multiple sclerosis (MS), focusing on three objectives: (1) Determine the impact of vocational rehabilitation and its effect size on employability for people with MS. (2) Identify specific components of vocational rehabilitation interventions associated with positive vocational outcomes in this population. (3) Describe work accommodations, facilitators, and barriers to vocational adjustment for people with MS.</p> Subject and method <p>Literature on the effect of vocational rehabilitation for individuals with MS was collected from multiple databases from inception to January 2024. Eligible experimental and quasi-experimental studies were included. A meta-analysis estimated the overall effect size, with subgroup analysis grouping studies based on outcome similarity.</p> Results <p>Eleven studies of moderate to low quality were included. Effective interventions included Cognitive Behavioral Therapy (CBT) and the Cognition-Targeted Exercise (CTE) Program, aquatic training, and education, among others. Effect sizes were calculated using <i>Cohen’s d</i> for various work-related outcomes. Interventions were most effective in two subgroups: reducing work-related difficulties (<i>n</i> = 4 studies; ES = 1.937, 95% CI = -0.664 to 4.537) and improving work modifications (<i>n</i> = 2 studies; ES = 1.204, 95% CI = 0.428 to 1.980). Regarding the qualitative outcomes, work accommodations and participant-tailored interventions effectively support employability among individuals with MS. Overall, vocational interventions had a significant effect on several work-related outcomes in people with MS.</p> Conclusion <p>Vocational rehabilitation effectively improves the employability of people with MS. Future research should prioritize high-quality RCTs and explore modern technologies.</p>