Persons experiencing homelessness and vulnerable housing or those with lived experience of homelessness have worse health outcomes than individuals who are stably housed. Structural violence can dramatically affect their acceptance of interventions. We carried out a systematic review to understand the factors that influence the acceptability of social and health interventions among persons with lived experience of homelessness.We searched through eight bibliographic databases and selected grey literature sources for articles that were published between 1994 and 2019. We selected primary studies that reported on the experiences of homeless populations interacting with practitioners and service providers working in permanent supportive housing, case management, interventions for substance use, income assistance, and women- and youth-specific interventions. Each study was independently assessed for its methodological quality. We used a framework analysis to identify key findings and used the GRADE-CERQual approach to assess confidence in the key findings.Our search identified 11,017 citations of which 35 primary studies met our inclusion criteria. Our synthesis highlighted that individuals were marginalized, dehumanized and excluded by their lived homelessness experience. As a result, trust and personal safety were highly valued within human interactions. Lived experience of homelessness influenced attitudes toward health and social service professionals and sometimes led to reluctance to accept interventions. Physical and structural violence intersected with low self-esteem, depression and homeless-related stigma. Positive self-identity facilitated links to long-term and integrated services, peer support, and patient-centred engagement.Individuals with lived experience of homelessness face considerable marginalization, dehumanization and structural violence. Practitioners and social service providers should consider anti-oppressive approaches and provide, refer to, or advocate for health and structural interventions using the principles of trauma-informed care. Accepting and respecting others as they are, without judgment, may help practitioners navigate barriers to inclusiveness, equitability, and effectiveness for primary care that targets this marginalized population.