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Background: Women who grow up in economic scarcity often face limited opportunities for upward mobility, as a result of challenges securing stable housing, quality education, and steady employment. Chronic instability may limit the capacity of women to protect themselves against HIV/STI-related harm when engaging in sexual activity or drug use. Characterizing the structural contexts that facilitate HIV/STI risk among women are critical to effective design and implementation of drug and sexual harm reduction interventions., Methods: Semi-structured in-depth interviews were completed with 25 female exotic dancers working in Baltimore City and County exotic dance clubs July 2014-May 2015. Using thematic analysis, interviews were examined to understand the nature of structural vulnerability experienced by dancers during their early lives through the initial months of exotic dancing, including an examination of the roles of drug use and social relationships in engagement of sexual risk behavior., Results: Dancers depicted early experiences of social and economic disadvantage, which accumulated through early adulthood. Substance use emerged as an important subject for the majority of women, operating cyclically as both precursor to and product of accumulating social and economic hardship. Dancers revealed social strategies that buffered the effects of structural vulnerability and minimized exposure to workplace-related drug and sexual harms., Conclusion: This study provides insight on an understudied group of at-risk women with a unique demographic profile. Findings illustrate how the effects of structural vulnerability, substance abuse, social strategies, and opportunities for economic gain through sexual services in the workplace converge to produce varying levels of HIV/STI risk among exotic dancers., (Copyright © 2017. Published by Elsevier B.V.)