Hepatitis C virus infection kinetics extrapolate complex crosstalk between viral proteins and host cell interactions by involving a plethora of genes and cell signaling to escape host immune responses and subsequently exacerbate the infection course. The approvals and the availability of oral, highly efficacious, and pan-genotypic direct-acting antivirals to treat chronic hepatitis C infection have raised the hopes of achieving the World Health Organization's ambitious goal of hepatitis C elimination by 2030. Several pitfalls exist in the current continuum of HCV care and certain gaps need to be filled for the successful implementation of HCV treatment and elimination strategies in highly endemic and vulnerable populations in many parts of the world in particular low to middle-income countries. This review aims to explore to what extent and to what capacity HCV kinetics, treatment-induced resistance associated substitutions (RASs), and crosscutting barriers of HCV genetic variabilities will impede the efforts and progress toward its elimination.