Purpose: To critically review the evidence for occupation-based interventions in improving occupational performance and participation outcomes in the hospital setting. Methods: Five databases were searched from 2000–2022. Peer-reviewed studies of any design investigating the impact of occupation-based interventions in the hospital setting were included. Methodological quality was assessed using the appropriate tool for each study design. Following data extraction, a narrative synthesis was conducted. Results: Thirty-three studies comprising of 26 experimental, five non-experimental, and two mixed methods studies were included (n = 1646 participants). Results indicate good evidence to support occupation-based interventions to improve occupational performance and participation outcomes in inpatient rehabilitation; it is unclear whether they are more effective than any control/alternative intervention. Research in the acute and mental health hospital settings were scarcer. Understanding the benefits of occupation-based interventions was enhanced through qualitative results including improving independence and confidence to discharge home, increasing motivation for therapy, connecting with others, and peer-based learning. Conclusions: Heterogeneity and methodological weaknesses across existing studies limits the conclusions that can be drawn on the impact of occupation-based interventions in the hospital setting. More rigorous research should be conducted with better reporting of intervention design and the use of robust measures of occupational performance.