A disproportionate number of street children use and inject drugs and engage in survival sex as coping mechanisms. This study aimed to determine the prevalence of drug use, injecting drugs, survival sex, and condom use and determinants associated with these behaviors among street children. Cross-sectional surveys were conducted in 2016 with an aim to sample 350 street children and youths in Kathmandu Valley, Nepal. Information about sociodemographic characteristics, injecting drugs, sexual risk behaviors, and biological specimens for HIV testing were obtained. The logistic regression model was used to identify the determinants associated with drug use, injecting drugs, survival sex, and condom use during last sex. Variables that were significantly associated with being a current drug user (versus never) in the presence of other variables included being a rag picker (adjusted odds ratio [AOR] = 3.2; 95% confidence interval [95% CI] = 1.73-5.9), history of imprisonment (AOR = 2.21; 95% CI = 1.21-4.04), alcohol consumption (AOR = 2.66; 95% CI = 1.46-4.84), and solvent sniffing (AOR = 5.12; 95% CI = 2.74-9.59). Variables that were significantly predictive of injecting drugs (versus never) in the presence of other variables include being 17 years old (AOR = 3.42; 95% CI = 1.11-10.55) and being a rag picker (AOR = 3.5; 95% CI = 1.25-9.75). Variables that were significantly associated with having survival sex (versus never) in the presence of other variables include being 17 years old (AOR = 3.58; 95% CI = 1.31-9.81) and having forced sex (AOR = 9.62; 95% CI = 3.21-28.8). Drug use and survival sex are major coping mechanisms among street children in Kathmandu Valley and are associated with many risk behaviors. Targeted programs should be implemented to meet their special needs.