Background: Drug and other substance abuse is a major important public health problem in Uganda affecting the adolescent’s mental growth and economic development which consequently impacts on their health and survival. In Uganda today, you can barely count the family, friends, and loved ones completely drawn to addictions. Promising students who pick habits from peers in school and forever loses their way, like an educated man who gets hooked to alcohol and ends up jobless, hopeless and useless to his family, and multiple young men in the suburbs becoming slaves to marijuana( Kidimu G. 2012). The main objective was to establish the determinants of drug and substances abuse among adolescents10-19 years in Katanga slum, Kampala district. Specific objectives were; to asses individual factors that lead to drug and substance abuse among adolescents 10-19 years in Katanga slum, Kampala district. To establish socio-economic factors that lead to drug and substance abuse among adolescent 10-19 years in Katanga slum, Kampala district. To asses community factors that influence drug and substance abuse among adolescent 10-19 years in Katanga slum, Kampala district. Methodology: A cross-sectional study was carried out with researcher administered questionnaires as a method of data collection from 280 respondents and 10 key informants. Descriptive bivariate analysis was undertaken into SPSS and frequency tables, graphs, pie charts and p values were generated using Epi Data software. Results: from the findings, 46.8% was the prevalence of drugs and other substances abuse among adolescents. The following were found to have a statistical significance with drugs and substances abuse; age (p=0.017), the single (p=0.001), received parental advice (p=0.006), how drugs are valued to them (P=0.001), adolescents showing off in public (p=0.002), parental influence to abuse drugs (p=0.001), easy accessibility (p=0.013), living in temporary homestead (p=0.001), and law enforcement practiced in the area (p=0.031). Conclusion and Recommendations: The study involved carrying out community health education, avoiding bad peer groups, parents guiding and being good example as far as drugs and other substances are concerned. The Ministry of Health collaborating with other stakeholders to introduce strategic policies on drug and other substances abuse preclusion especially in slums. Further research should be done on how to bridge the gap between adolescents abusing drugs and other substances and the stakeholders like government and Nongovernmental organizations to join hands in the abuse fight campaign.

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