Background: Persons impacted by homelessness or housing instability often suffer from serious infectious and chronic conditions. Objectives: The systematic review examined the intersection between homelessness, STIs, risk factors, and existing prevention/intervention evidence. Methods: Peer reviewed articles (N=251) published 2000-2011 related to sexual health risk, outcomes and homelessness were identified. 77 articles met a five point criteria for inclusion. International studies and those without STI prevalence data for homeless persons were excluded for a final dataset of 34 articles. Dataset populations were: adolescents (n=10), women (n=9), men (n=1), nondescript adults (n=9), LGBT (n=4), and veterans (n=1). Descriptive and qualitative analyses included: STI prevalence ranges by population and factors associated with homelessness, sexual risk, prevention and treatment measures. Results: STI prevalence ranged 4.7% to 27%. STI risk factors across subgroups included: inconsistent condom use, survival sex, and substance use/abuse. In adolescents, STIs were higher among females; males were more likely to engage in anal and anonymous sex. LGBT persons had greater HIV risk, but were more likely to report being tested for STIs. Women were more likely to report risky sex in abusive relationships, have unrecognized HIV infection and recent STI diagnoses. Among men, risk behaviors were associated with homelessness severity and PTSD. A higher prevalence of HIV infection was reported for adults who participated in exchange sex (7.3% men; 9.1% women). Conclusions: STI infection among homeless persons is associated with unstable housing, high risk events, circumstances, and behavior. Housing and stability can reduce global risk reduction. Sexual health prevention interventions may enhance supportive housing and stabilization efforts. Implications for Programs, Policy, and Research: Enhancing sexual health within the context of homelessness should be better understood and translated into effective interventions programs that can reduce STI risk during various stages homelessness and housing re-stability.