BackgroundRisks for condomless sex among transgender women and cisgender men who have sex with men (trans-WSM and cis-MSM, respectively) in the Philippines, where HIV recently became a national public health crisis, are shaped and exacerbated by various risk factors across multiple levels.MethodsBetween June 2018 and August 2019, we conducted a cross-sectional online study with 318 trans-WSM and cis-MSM respondents from Manila and Cebu cities. Structural equational modelling procedures were performed to determine direct, indirect and overall effects between condom use and latent variables across multiple socioecological levels: personal (ie, condom self-efficacy), social (ie, social capital), environmental (ie, barriers to condom and HIV services) and structural (ie, structural violence, antidiscrimination policies).ResultsAdjusted for gender, age, location and income, our model showed that: (1) all latent variables at the structural and environmental levels were significantly positively associated with each other (all ps<0.05); (2) barriers to condom and HIV services were significantly negatively associated with social capital (p<0.001) as well as condom self-efficacy (p<0.001); and (3) there were significantly positive associations between social capital and condom self-efficacy (p<0.001), and between condom self-efficacy and condom use (p<0.001). Moreover, social capital and condom self-efficacy fully mediated and buffered the negative effects between environmental and structural barriers and condom use.ConclusionThis is the first known study pointing to multiple relationships and pathways across multiple socioecological levels that can potentially be leveraged for future interventions aimed at improving condom use among Filipinx trans-WSM and cis-MSM. Such interventions should be multicomponent and build and/or strengthen social capital and condom self-efficacy, as well as intentionally target prominent structural and environmental barriers to condom use.