Illicit drug use is a growing concern in India, with a high treatment gap of 73%. Explanatory models can provide valuable insights into the patient’s conception of disease and inform help-seeking, treatment, and recovery. Of the studies that examine adolescent drug misuse in India, none have developed a socio-cultural explanatory model. The aim of our study was to develop an explanatory model to better understand the causal beliefs, social context, and self-perception of illicit drug misuse amongst adolescents in India. We conducted semi-structured interviews with 23 adolescents seeking treatment for drug use disorders and 25 healthcare providers recruited across three sites in India. Thematic analysis was used to analyse data. Most adolescent participants reported using multiple drugs, often in combination with cannabis. Frequent usage was reported i.e., daily at multiple times. Causes of initiation and continued use were peer influence, curiosity and pleasure, psychosocial stressors, family conditions, and systemic risk factors (e.g. socioeconomic instability). Drugs were acquired from various sources, including fellow users and pharmacies. Adolescent participants perceived negative impacts of drug use on physical and mental health, family relationships, and everyday functioning. Our findings on common reasons of drug use initiation, importance of peer relationships in continuation of use, impact of use on various aspects of life and the relationship of illicit drug use with socioeconomic status are consistent with previous research done in India on the subject. Understanding how adolescents and caregivers perceive drug use can help inform patient-clinician rapport, improve treatment compliance and understand intervention effectiveness. Such an explanatory model holds crucial implications for shaping interventions and clinical approaches to address adolescent drug use in India.