Polydrug use is caused by multiple factors within the polydrug users’ ecological system resulting in polydrug dependency, a complex behavioural disease with chronic features. This paper, guided by the social learning theory, seeks to examine some of the causal factors that lead patients undergoing therapy in Methadone assisted Therapy [MAT] clinics in Nairobi County to polydrug use. The study uses a mixed methods approach utilizing both quantitative and qualitative data collection methods in a quasi-experiment. The experiment entailed pre and post-strategy for the experimental group at site A and the control group at site B, where both groups underwent baseline and end-line assessment for MAT treatment. The study population consisted of 2121 patients drawing a sample size of 120 respondents through random sampling. The end-line assessment was done using the same tools after three months during follow-up. Data analysis was done descriptively and by inferential statistics to correlate the various factors. The findings are presented in tables and indicate that biological factors, history of polydrug use within MAT patients’ families, spiritual and existential factors, and MAT patients’ missing Methadone dosage were statistically significant to polydrug use.