Background <p>In the landscape of sexual health, sex, gender, and sexuality are inextricably linked and highly relevant to sexually transmitted infections (STIs). Globally, key sexual and reproductive health concerns of women have been associated with the socioeconomic status of their country, indicating that social context bears influence over sexual health outcomes. Further, the increasing prevalence of antimicrobial resistant STIs (AMR-STIs) in the sexual networks of gay and bisexual men-who-have-sex-with-men (GBMSM) suggests an implicit connection between microbiological and social phenomena, although research to date is relatively limited and often fails to reflect the complexity and nuance of sexual networks. Vulval and vaginal microbiome composition may influence STI acquisition and transmission, yet the relationships between composition, microenvironment, and STIs remain largely overlooked, especially in the context of women and gender-diverse people. In this article, we explore the possibility that a combination of social, sexual, and behavioural factors, combined with biological features, shape the microbiological context of STIs within the vaginal microenvironment.</p> Main <p>The human vaginal microbiome (VMB) forms an ecological niche home to a complex ecosystem of microorganisms. The microbial composition of the VMB is diverse between individuals, with variations observed across racial and ethnic groups, and intrapersonal fluctuations linked to a plethora of factors both within and outside of personal control. Importantly, VMB health is a crucial component of wellbeing for people assigned female at birth (AFAB), transgendered women with neovaginas, and their sexual partners. Clinical context also remains important; in Australia, doxycycline prophylaxis (Doxy-PEP) has recently become available to GBMSM networks aimed to protect against the acquisition of STIs. However, Doxy-PEP guidelines exclude AFAB people and fail to specify regarding use among gender diverse individuals. Given the high prevalence of AMR-STIs within GBMSM networks, the impact of this intervention on excluded partners should be thoroughly investigated. Factors in the VMB such as biofilm formation and necessary microbial balance with opportunistic pathogens renders this ecological microbial niche a hypothetically perfect platform for AMR development and emergence within the social context.</p> Conclusion <p>This review explores the social context of vaginal microbiomes, their potential influence on AMR-STI development, and highlight several important knowledge gaps to benefit from further research.</p>