<p>Hepatitis B virus (HBV) is a global public health threat. It has been linked to the development of cirrhosis and hepatocellular carcinoma (HCC) which may lead to different types of liver damage. This review explores the intricate biology of HBV, emphasizing the structure and life cycle of the virus and the role of viral RNAs. Even though new antiviral medications like pegylated interferons alpha and nucleos(t)ide analogues (NA), have been confirmed to be efficient in inhibiting HBV replication, but the developing resistance, side effects of existing drugs and lack of potency to reduce covalently closed circular DNA (cccDNA), are worrisome and indicate the need of new drug development. A thorough understanding of the host virus interaction and the mechanism of immune evasion for viral persistence will help to identify the new drug targets. Currently available vaccines have proven to be effective in the prevention of HBV infection, but the current ongoing research aims to enhance their protection duration, efficacy, and accessibility, using new regimens. The new antiviral/vaccine strategies that have emerged from different discoveries, highlight the significance of further research to create efficient treatments that can accomplish long-term viral suppression and eventually aid in the treatment of HBV infection. The current review summarizes, the understanding of the mechanism of viral replication, different targets for drug development, and strategies to develop the potential vaccine candidates to combat HBV infection.</p>