Introduction Social determinants of health have immense influence on the overall health outcomes of individuals. Homelessness, when set within the context of the socioecological model, includes relevant individual/personal factors like such as substance use and depression, social/interpersonal factors such as stigma, and structural factors including subsistence needs and access to health care or utilization of health care. These 3 types of factors influence adherence levels to antiretroviral therapy. Objective To identify associations between homelessness and antiretroviral therapy adherence and relationships between other modifying variables associated with housing status and treatment adherence. Methods A literature search was conducted using PubMed from 2000 to 2023. A total of 10 articles from this search were identified as appropriate for inclusion, with an additional 2 articles added from parsing references in already approved articles. Results The literature supports a negative association between homelessness and adherence to antiretroviral therapy. Additionally, a variety of factors were found to modify adherence levels in people living with HIV experiencing homelessness, with increased access and reduced barriers to health care mitigating the effect of homelessness on adherence, while unfulfilled subsistence needs reduce adherence levels. An identified intervention in the literature was supportive housing, which entails the provision of housing to those experiencing homelessness to improve their HIV-related health outcomes. Conclusions Among urban populations in the United States, homelessness and other relevant factors had a significant association with reduced adherence levels to antiretroviral therapy in people living with HIV.