Hepatitis B (HBV) prevalence is very high in pregnant women in the Dolpa district of Nepal, a region characterised by a remote geographic landscape and low vaccination coverage. Using mathematical modelling, we evaluated the impact of third-trimester tenofovir disoproxil fumarate (TDF) prophylaxis on HBV burden and estimated the time required to achieve HBV elimination in Dolpa. We developed a mathematical model to assess the impact of TDF prophylaxis on HBV elimination under four scenarios: baseline 50% vaccination coverage (scenario I), 50% TDF and baseline vaccination coverage (scenario II), 90% TDF plus baseline vaccination (scenario III) and 90% TDF and birth-dose plus 95% vaccination coverage (scenario IV). We estimated the impact TDF prophylaxis has on HBV-related morbidity and mortality and projected the time required for HBV elimination in the district. Our model suggests that HBV elimination is unlikely in Dolpa by 2100 under baseline interventions. The scale-up of TDF coverage to 90% with the baseline vaccination significantly reduces HBV prevalence and HBV-related mortality, making elimination possible in <60 years. Implementing 90% TDF alongside birth-dose vaccination and 95% infant HBV vaccination coverage could accelerate HBV elimination\u2014\u22640.1% HBV prevalence in children younger than 5 years\u2013achieving it by 2045. In geographically inaccessible settings, a micro-elimination approach using third-trimester TDF is an effective and equitable strategy for HBV control. This approach is likely to substantially reduce HBV burden and HBV-related mortality even before achieving elimination, while also addressing some of the challenges of immunoprophylaxis.<\/p>\n\r\n