This study investigated the clustering of psychosocial adversities and their synergistic effect with depression on suicidality in a 12-month prospective cohort (N = 214) of YMSM living with HIV in Bangkok, Thailand. Latent class analysis identified subgroups with distinct combinations of adversities, including bullying, intimate partner violence, substance use, HIV stigma, low social support, histories of sex work, and below-income status. Significant interactive synergism were found as hypothesized, supporting a syndemic effect with qualitatively increasing levels of adversities on suicidality (score range: 3-17) over the 12 months. The interaction between moderate adversity clustering and depression (β = 2.50, 95% CI: 1.12-3.88) and high adversity clustering and depression (β = 3.61, 95% CI: 1.12-6.09) indicated that the impact of depression on suicidality was modified by pre-existing adversities. The findings suggest that, while a multi-component intervention addressing psychosocial problems is ideal, effective depression treatment alone could significantly reduce suicidality among YMSM living with HIV.