The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled prevalence of hepatitis E across countries within the Southeast Asian region by the UN division. A comprehensive systematic database search was conducted across PubMed, Web of Science, and Scopus databases, supplemented by a manual search in Google Scholar. Studies that presented seroprevalence data of hepatitis E virus (HEV) in Southeast Asian nations were eligible for inclusion, and a meta-analysis was subsequently conducted. The assessment of bias risk was undertaken using the Joanna Briggs Institute checklist. The ensuing meta-analysis provides an evaluation of 66 chosen studies from a pool of 1641, encompassing a total cohort of 44,850 individuals from Southeast Asian countries. The pooled prevalence of anti-HEV IgG within Southeast Asian countries was determined to be 21.03%. Stratification of the study population based on the risk of HEV acquisition into two cohorts—high-risk and low-risk groups—yielded a pooled anti-HEV IgG prevalence of 28.9%, with an accompanying IgM prevalence of 4.42% in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively. A temporal analysis, segmented into three distinct decades (1987–1999, 2000–2010, 2011–2023), indicated an uprising trend in both IgG and IgM prevalence over the specified time spans. These findings contribute to a better understanding of HEV prevalence across populations and time periods in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies.