Entrenched economic and gender inequities together are driving a globally expanding, increasingly female, HIV/AIDS epidemic. To date, significant population-level declines in HIV transmission have not been observed at least in part because most approaches to prevention have presumed a degree of individual control in decision-making that does not speak to the reality of women's and girls' circumstances in many parts of the world. Such efforts have paid insufficient attention to critical characteristics of the risk environment, most notably poverty and gender-power inequities. Even fewer interventions have addressed specific mechanisms through which these inequities engender risky sexual practices that result in women's disproportionately increased vulnerabilities to HIV infection. This paper focuses on identifying those mechanisms, or structural pathways, which stem from the interactions between poverty and entrenched gender inequities and recommending strategies to address and potentially modify those pathways. We highlight four such structural pathways to HIV risk, all of which have the potential to be transformed: 1) lack of access to critical information and health services for HIV/STI prevention; 2) limited access to formal education and skills development; 3) intimate partner violence; and 4) the negative consequences of migration prompted by insufficient economic resources. We argue for interventions that enhance women's access to education, training, employment, and HIV/STI prevention information and tools; minimize migration; and by working with men and communities, at the same time reduce women's poverty and promote gender equitable norms. In conclusion, we identify challenges in developing and evaluating strategies to address these structural pathways.