Objective: This study aims to review and synthesize the empirical evidence about the connection between healthcare facility design and the mental health of healthcare professionals by reviewing the relevant literature. Background: Mental exhaustion of healthcare professionals is becoming a critical issue in healthcare, especially during the pandemic. The physical design of healthcare facilities has significant potential to reduce and prevent the mental exhaustion of healthcare professionals by removing environmental stressors and providing restorative experiences. However, the built environment is not fully utilized as an intervention to support healthcare professionals. Methods: Relevant articles were identified from the Medline, PsycINFO, PubMed, and Web of Science databases using a combination of search terms representing environmental design factors and health outcomes. Identified articles were reviewed by their titles, abstracts, and full texts using the inclusion and exclusion criteria. Results: The search yielded 27 empirical articles investigating the relationships between environmental design factors and staff mental health outcomes, including stress, fatigue, job satisfaction, burnout, and well-being. Healthcare design aspects that were investigated in the identified articles include overall facility and perception (e.g., aesthetic appeal and impression, belonging to the surroundings, safety), specific spaces (e.g., patient area, staff workspace), intangible elements (e.g., exterior view, light, sound), and interior space and ergonomics (e.g., material finishes, furniture). Conclusions: Through the synthesis of the current literature regarding the relationships between healthcare facility design and the mental health of healthcare professionals, this study provides implications for supporting healthcare professionals through the design of the healthcare facility.