Hepatitis C virus (HCV) remains a significant global health challenge, affecting approximately 50 million people worldwide as of 2024. The advent of direct-acting antivirals (DAAs) has significantly improved treatment outcomes, with cure rates exceeding 90%. However, challenges such as regional disparities in DAA access, variable response rates, and the emergence of resistance-associated substitutions (RASs) persist. This comprehensive review integrates the latest knowledge on HCV epidemiology, pathophysiology, diagnostic approaches, treatment options, and preventive strategies, focusing on the challenges posed by RASs and ongoing vaccine development efforts. The review aims to provide healthcare professionals, researchers, and policymakers with insights to address the HCV burden more effectively, aligning with global health objectives to reduce chronic hepatitis and eliminate HCV as a public health threat by 2030. Key topics include the history of HCV, its genetic diversity, pathogenesis, clinical features, diagnosis, treatment, and prevention strategies. The review highlights the progress made in managing and preventing HCV infection while addressing persistent barriers to its prevention.Hepatitis C virus (HCV) remains a significant global health challenge, affecting approximately 50 million people worldwide as of 2024. The advent of direct-acting antivirals (DAAs) has significantly improved treatment outcomes, with cure rates exceeding 90%. However, challenges such as regional disparities in DAA access, variable response rates, and the emergence of resistance-associated substitutions (RASs) persist. This comprehensive review integrates the latest knowledge on HCV epidemiology, pathophysiology, diagnostic approaches, treatment options, and preventive strategies, focusing on the challenges posed by RASs and ongoing vaccine development efforts. The review aims to provide healthcare professionals, researchers, and policymakers with insights to address the HCV burden more effectively, aligning with global health objectives to reduce chronic hepatitis and eliminate HCV as a public health threat by 2030. Key topics include the history of HCV, its genetic diversity, pathogenesis, clinical features, diagnosis, treatment, and prevention strategies. The review highlights the progress made in managing and preventing HCV infection while addressing persistent barriers to its prevention.