Using data from a qualitative study and a subsequent quantitative survey among 918 male and transgender sex workers (MTSW), we explore the context of multiple risks they face. We show that over one-fifth of MTSW have sex with IDU clients. Combined with high levels of risk behavior and very low levels of risk reduction and knowledge, the extent of sexual networking with men who inject drugs contributes further to the sex workers' health risks. Our findings suggest that isolated interventions with single-risk groups are unlikely to be sufficient to control the spread of the epidemic in Pakistan. We highlight the need for integrated approaches to risk reduction programs among MTSW and IDUs.