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Global evidence indicates that multiple structural, biological, and behavioural mechanisms link gender-based violence (GBV), HIV/HCV, and substance misuse among women and adolescent girls. The aim of this chapter is to briefly summarise and synthesise recent literature that examines the complex and bi-directional relationships among these epidemics in different populations of adolescent girls and women around the world. To inform this chapter, a selective search strategy was conducted, prioritising use of meta-analytic epidemiological studies and research on interventions and policies that address different aspects of the syndemic among women and girls who use drugs worldwide. The search targeted publications from 2015 to 2019 using PubMed, MEDLINE, and Google Scholar. The chapter highlights methodological and geographic gaps in existing policy, intervention, and implementation research and makes recommendations for strategies to tackle these gaps. It also identifies a continuum of multilevel evidence-based interventions that target the risk environments and key syndemic mechanisms linking these intersecting epidemics that have been found to be effective in reducing intimate partner violence and other forms of GBV, substance use, and HIV/HCV risks. This chapter also assesses inclusiveness of existing research and interventions for underserved and disproportionately affected populations, affecting adolescent girls, sexual minority women, and racial/ethnic minority women and identifies strategies to target gaps or disparities for these key affected populations. Finally, this chapter describes the gaps and opportunities that harm reduction programmes, medical settings, and other community organisations experience in implementing gender-responsive programmes and policies to redress these intersecting epidemics.