Background and Objectives: A syphilis outbreak and overdose/toxic drug poisoning (TDP) emergency have been declared in the province of British Columbia (BC), Canada. In Fraser Health Authority (FHA), BC’s largest regional health authority, rates of infectious syphilis and TDP events have increased among women since the start of the COVID-19 pandemic. We aim to understand social and structural factors associated with the emergent syndemic of women affected by infectious syphilis and TDP to inform targeted interventions and improve service provision. Methods: The data source was a retrospective chart review of all women-identified individuals diagnosed with infectious syphilis in FHA from January 2021 to April 2022 from hospital records and public health databases. We used Latent Class Analysis (LCA) to identify subgroups based on patterns of socio-demographic factors (e.g. unstable housing), comorbidities (e.g. mental health disorders), and health service utilisation. Results: A total of 113 women were included, of whom 61% were ever diagnosed with an opioid- or stimulant use disorder and 30% had an emergency department visit for TDP. We identified three subgroups by LCA: 1. “Incarceration experience, co-morbidities” (n=22, 19%): incarceration (100%), mental health disorder diagnosis (96%), stimulant use (86%), income assistance (59%), 2. “Multiple barriers, child removal” (n=37, 33%): concurrent opioid and stimulant use (78%), child removal (55%), intimate partner violence (46%), 3. “Greater resiliency factors” (n=54, 48%): attached to primary care practitioner (57%), syphilis diagnosed during pregnancy (19%). Conclusions: Two subgroups (52% of the sample) were highly impacted by mental health, substance use challenges and structural vulnerabilities, which may results from social and systemic inequities driving the syndemic. Enhancing women-centred health services addressing sexual health, mental health and determinants of health may increase opportunities for engagement, prevention and harm reduction. An additional subgroup (48%) had fewer structural vulnerabilities, and further analyses are needed to better elucidate their distinct care needs.