Work is a growing concern in disability and rehabilitation fields. Specific evidence related to occupational therapy in the area of vocational rehabilitation is somewhat limited. With increased demands for occupation-focused, evidence-based, and theory-informed practice, this review aims to use clinically relevant questions to organize and synthesize evidence regarding work-related interventions specifically related to an occupation-focused theory, the Model of Human Occupation. A total of 45 published works related to both the MOHO and vocational issues were identified and included in the review. The review demonstrates that there is a range of evidence that supports the use of the MOHO and its tools as a basis for work-based clinical interventions. Evidence supports the conclusion that MOHO-based work assessments have good psychometric properties and are useful in evaluating vocational potential and needs. MOHO-based work programs have been shown to have a positive impact in improving vocational outcomes to a range of clients.