Women and girls continue to experience disproportionate HIV vulnerability across regions marked by deep-rooted gender inequality and economic insecurity. While biomedical advances have expanded prevention options, the structural determinants particularly poverty, economic dependence and limited financial autonomy remain under-addressed drivers of HIV risk. Economic vulnerability reduces women’s bargaining power, heightens exposure to gender-based violence and restricts access to HIV prevention and treatment services. Emerging evidence shows that economic empowerment interventions including cash transfers, savings groups, livelihood programs and financial literacy training can reduce HIV risk behaviors and enhance agency. This commentary argues that economic empowerment must be recognized as a central pillar of HIV prevention and care beyond a peripheral development issue. Integrating economic strengthening within sexual and reproductive health and HIV programs offers a gender-transformative pathway to reduce vulnerability and improve long-term outcomes. Achieving global HIV targets requires confronting economic inequities as core health challenges.