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Female entertainment and sex workers (FESW) are vulnerable to violence, which impedes safer sex behaviors and increases risk of HIV. FESW are also disproportionately affected by co-occurring psychosocial health conditions, including substance use, depression, and economic insecurity, which increased risk of exposure to violence. We used a syndemic framework to examine the effects of co-occurring psychosocial conditions on the risk of client-perpetrated physical and sexual violence against FESW. Data were collected among 1198 Cambodian FESW on recent client-perpetrated physical and sexual violence, and psychosocial conditions (psychological distress, alcohol consumption, amphetamine-type stimulant (ATS) use, debts, housing, and food insecurity). Bivariate and multivariate logistic regressions were conducted. Prevalence of physical and sexual violence from clients was 4.8% and 6.9%, respectively. Client-perpetrated physical violence was associated with housing insecurity, ATS use, and psychological distress. All psychosocial conditions, except ATS, were associated with exposure to sexual violence. In multivariable models, odds of client-perpetrated physical violence were twice higher among women with ≥ 4 compared to ≤ 3 psychosocial conditions. Risk of sexual violence increased with the number of psychosocial conditions. Compared to those with ≤ 1 condition, FESW with two psychosocial conditions had twice the odds (AOR = 2.08; 95% CI 1.00-4.31) and women with 5-6 psychosocial conditions had eightfold higher odds (AOR = 8.10; 95% CI 3.4-19.31) of sexual violence from clients. Our findings support a syndemic model of co-occurring psychosocial conditions among FESW that are associated with increased risk of violence. Violence prevention interventions targeting FESW should adopt comprehensive approaches that address co-occurring psychosocial conditions.