Background: The hepatitis B virus (HBV) poses a significant global health threat, with 240–350 million chronic infections and 1.3 million deaths yearly. In Ethiopia, the prevalence of HBV among pregnant women was recorded to be between 2.3% to 7.8% from 2014 to 2018, indicating a widespread issue. Despite existing knowledge about risk factors, the high prevalence of HBV infection among pregnant women persists, and effective prevention strategies have yet to be determined. This study aims to develop and implement strategies to effectively prevent HBV transmission among pregnant women in Ethiopia. Methods: The study was conducted in four healthcare facilities in the Tigray regional state of Ethiopia. It consisted of three phases: Phase 1 involved an integrative literature review to explore best practices in preventing HBV infection among pregnant women. Phase 2 focused on exploring the perceptions and views of pregnant women and healthcare workers regarding HBV prevention measures among pregnant women in Ethiopia. Phase 3 involved the development and validation of strategies to promote the prevention of HBV transmission among pregnant women in Ethiopia. The study included pregnant women receiving antenatal care services and healthcare workers providing these services. The sample size for each group was determined using the saturation principle. Data was collected through semi-structured interviews and focus group discussions. Field notes were taken during the interviews, and the interviews were audio recorded with participants' permission. Tesch’s method of data analysis was used. Results and Discussions: According to a review of twelve studies, it is crucial to screen pregnant women for HBV infection during the first trimester to prevent mother-to-child transmission (MTCT) and identify infected partners. In areas with high HBV prevalence, most infections occur due to MTCT in early childhood. Based on our research, routine screening of pregnant women during each prenatal visit is a good strategy to break the cycle of HBV infection and decrease the impact of MTCT. Additionally, nine studies have reported that maternal antiviral prophylaxis and therapy for pregnant women infected with HBV are effective strategies to prevent disease transmission. Qualitative data collected from pregnant women and healthcare workers indicated a low level of knowledge, attitude, and practice regarding HBV prevention and control activities. Conclusions: This comprehensive study delves into the perspectives of pregnant women and healthcare workers regarding HBV infection and its prevention strategies. Additionally, it explores the most effective practices for preventing HBV infection in pregnant women. These strategies have been rigorously validated using a SWOT analysis framework and through extensive consultative meetings with various stakeholders. Furthermore, the study recommends further qualitative research on the drivers of HBV infection.