This scoping review aims to provide a comprehensive overview of human melioidosis in Southeast Asia as well as to highlight knowledge gaps in the prevalence and risk factors of this life-threatening disease using available evidence-based data for better diagnosis and treatment. Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) was used as the guideline for this review. The literature search was conducted on 23 March 2022 through two electronic databases (PubMed and Scopus) using lists of keywords referring to the Medical Subject Headings (MeSH) thesaurus. A total of 38 articles related to human melioidosis were included from 645 screened articles. These studies were carried out between 1986 and 2019 in six Southeast Asian countries: Thailand, Cambodia, Malaysia, Myanmar, Singapore, and Vietnam. Melioidosis has been reported with a high disease prevalence among high-risk populations. Studies in Thailand (48.0%) and Cambodia (74.4%) revealed disease prevalence in patients with septic arthritis and children with suppurative parotitis, respectively. Other studies in Thailand (63.5%) and Malaysia (54.4% and 65.7%) showed a high seroprevalence of melioidosis among Tsunami survivors and military personnel, respectively. Additionally, this review documented soil and water exposure, diabetes mellitus, chronic renal failure, thalassemia, and children under the age of 15 as the main risk factors for melioidosis. Human melioidosis is currently under-reported in Southeast Asia and its true prevalence is unknown.