Parental substance dependency‟ a parent-dependent stressor for offspring, has an immense impact especially on adolescents. Being in a critical bio-psycho-socio transitional development phase of life, adolescents with substance dependent parents have to experience several negative life events that potentially can increase vulnerability to grow psychological distress within them. Families with substance dependent parents are usually found to have higher levels of interpersonal conflicts, physical aggression towards partners and children, poor parenting and significantly higher levels of trauma, depression and anxiety in offspring, compared to substance non-dependent parents. Although a number of research works have been done in western world so far on substance dependent parents and their children in various dimensions, yet in our culture research works are still mostly focused on prevalence, causes, relapse factors, etc. which are related to drug dependency problem itself. In present case-control study method was followed. It was attempted to examine the psychological distress and coping strategies among the adolescents of substance dependent parents. All participants (M= 13.63; SD=1.61) of cases (adolescents with substance dependent parents) and controls (adolescents with substance non-dependent parents) were unmatched. Both groups (139 cases and 278 controls) were drawn from a study population of 650. Both groups of adolescents completed four measures on depression, anxiety, stress reactions and coping strategies. Adolescents from case group scored higher on psychological distress, whereas, adolescents with substance dependent parents were more depressed, anxious and had high elevated risk of developing post-traumatic stress disorder. In coping with the parental substance dependency adolescents from case group used more active coping and negative coping strategies whereas, adolescents with substance nondependent parents used more active and avoidant coping. The strongest predictors of psychological distress among adolescents were parental substance dependency, coping strategies (mostly avoidant and negative coping), socio-economic status, gender, educational status and achievement of adolescents and parental history of chronic relapse. The findings uphold the psychological state of adolescents with parental substance dependency that demand more intensive intervention and prevention program to reduce the vulnerab ility among these adolescents. we recommend to conduct various research studies on such vulnerable psychological areas of the adolescents so that pathways to create a socio-cultural context that is essentially supportive and helpful for them to recover permanently from existing psychological problems and become resilient to any future vulnerabilities.