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Background: People experiencing homelessness (PEH) often face mental illnesses such as schizophrenia, anxiety, bipolar disorder, and substance use disorder. They are also more likely to utilize the emergency department (ED) rather than primary care providers. Homelessness interventions vary, including strategies such as incentive-based strategies, rehabilitation services, case management, and Housing First (HF). Objective: The objective of this research is to compare the effectiveness of HF to treatment-asusual (TAU) in reducing ED use among PEH with concurrent mental illness. Methods: PubMed and Medline databases were searched for randomized controlled trials published in the past 10 years. Studies were screened using predefined criteria and assessed for quality using The National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool. Data was analyzed to determine clinical significance. Results: Four randomized control trials (RCTs) from France, Canada, and the United States were analyzed for this systematic review (SR). The studies provided mixed results with respect to how the HF model impacts PEH with mental illness and their ED use. Conclusion: HF did not demonstrate superiority over TAU in reducing ED visits among PEH with mental illness. However, it has proven to be a valuable intervention for improving health outcomes in this population.