We initially screened 754 healthy individuals for anti-HCV, consisting of 415 females and 339 males, using cluster random sampling method. The overall active prevalence of HCV in apparently healthy individuals was found 19.2% (145 individuals) in the underprivileged population of Islamabad, Pakistan. We found higher prevalence in females as compare to males. Among the most common risk factors responsible for the transmission of HCV were history of caesarean section and piercing, low literacy rates, gender, marital status, risk from HCV infected individuals within the family, circumcision and previous history of dental surgery. We assessed the role of different factors, e.g. gender, age, IL28B (rs12979860) polymorphism and viral genotype that could affect the therapy response. We reported that only IL28B (rs12979860) had strong association with positive treatment outcomes. After six month of combined therapy of ribavirin and interferon, 20 patients were positive for HCV while 47 people cleared HCV RNA. The most dominant genotypes were HCV-3a (62.68%), followed by HCV-1a (26.86%) and untypable HCV (10.44%) genotype in underprivileged areas of Islamabad. CC (81.57%) was the most prevalent followed by CT (55.55%) and TT (9%) rarest polymorphism. Our study also included a unique case of multidrug resistant HCV patient. The patient was scrutinized for IL28B polymorphisms [rs12978960 (CT), rs8099917 (GT)] to discover the resistant nature of HCV to antiviral therapy. Several reports have shown mutations associated with resistance to modern antiviral like sofosbuvir. In addition, sequencing, phylogenetic analysis, molecular modelling and docking of NS3 protein was also carried out. In the present study, 3D structure of NS3 of HCV genotype 3a, isolated from infected patient, was reported for the first time. Keeping in view the importance of protein-inhibitor interactions, we successfully identified a potent inhibitor against NS3 model using molecular docking approach. Compound 1 predicted in the current study, showed high binding affinity against the modelled protein. Compound 1found binding inside the ATP binding site with few residues of helicase domain of NS3. It also developed hydrogen bond interactions unlike FDA approved (Telaprevir and Boceprevir) NS3 protease inhibitors. The study can serve as model to design dual antiviral inhibitors against other HCV genotypes in future.