This study evaluated a cumulative and syndromic relationship among commonly co-occurring vulnerabilites (homelessness, incarceration, low-income, residential transition) in association with HIV-related risk behaviors among 635 low-income women in Baltimore. Analysis included descriptive statistics, logistic regression, latent class analysis and latent class regression. Both methods of assessing multidimensional instability showed significant associations with risk indicators. Risk of multiple partners, sex exchange, and drug use decreased significantly with each additional domain. Higher stability class membership (77%) was associated with decreased likelihood of multiple partners, exchange partners, recent drug use, and recent STI. Multidimensional social vulnerabilities were cumulatively and synergistically linked to HIV risk behavior. Independent instability measures may miss important contextual determinants of risk. Social stability offers a useful framework to understand the synergy of social vulnerabilities that shape sexual risk behavior. Social policies and programs aiming to enhance housing and overall social stability are likely to be beneficial for HIV prevention.