INTRODUCTION: Treatment of hepatitis B virus (HBV) infection primarily relies on nucleos(t)ide analogues to achieve viral suppression, with tenofovir or entecavir as first-line agents. Expanding treatment and improving its outcomes are crucial strategies to support progress towards global viral hepatitis elimination targets. However, therapeutic drug monitoring has not been optimized for HBV therapy. METHODS: We conducted a systematic review (PROSPERO CRD420250599139) to identify studies reporting on the relationship between drug concentrations and treatment outcomes of HBV in English from PubMed, Scopus and Web of Science. Primary search included people living with HBV, with or without HIV coinfection, treated with tenofovir and/or entecavir, and linked to treatment outcome. RESULTS: Six studies were included, of which five reported on HIV/HBV coinfection, and one on HBV monoinfection. Across studies, tenofovir concentrations >800 fmol/punch in dried blood spots were typically associated with viraemic suppression for both HIV and HBV. Evidence suggests that higher tenofovir concentrations (e.g. 1000-1500 fmol/punch) may be required for consistent HBV suppression. DISCUSSION: A therapeutic threshold cannot currently be defined for concentrations of tenofovir or entecavir in HBV. Larger cohort studies focusing on HBV monoinfection are needed to define therapeutic drug thresholds to optimize personalized care for people living with HBV.