Background: In Latin American countries and Suriname, sexual transmission is one of the most common modes of HIV transmission, and men who have sex with men (MSM) who engage in sex work constitute a key population. Methods: In a sample of MSM (N = 53,166) from the Latin American Internet Survey (2018) across 18 countries, we examined how sex work engagement is associated with syndemic conditions (multidrug use, homophobic abuse, depression/anxiety, alcohol dependency (CAGE alcohol questionnaire) and internalised homonegativity) and condomless anal intercourse with non-steady male partners using separate logistic regressions. We then used a structural equation model to determine if and how syndemic conditions mediate the relationship between sex work engagement and non-steady male partners. Results: We found that getting paid for sex was associated with less condom use for anal intercourse with non-steady male partners and particular syndemic conditions, such as multidrug use, homophobic abuse and alcohol dependency. In our structural equation model, the results showed that the direct relationship between sex work engagement and non-steady male partners was positive and significant, and syndemic conditions partially mediated this relationship. Conclusion: Our results highlight the continuing need for including MSM who engage in sex work and those who experience syndemic conditions in the prevention strategies targeted to MSM in Latin America and Suriname, to prevent the transmission of HIV.