The use of e-cigarettes in adolescents remains a major public health concern. Like other tobacco products, e-cigarettes pose health risks to adolescents. Understanding the magnitude of this problem and identification of its associated factors will serve as a guide for development of preventive interventions. This systematic review aims to identify and discuss current epidemiological data on the prevalence and associated factors of e-cigarette use among adolescents in Southeast Asia. The reporting of this systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. We carried out a literature search through three databases (Scopus, PubMed, Web of Science) and targeted original English-language articles published between 2012 and 2021. A total of 10 studies were included in this review. The prevalence of current e-cigarette uses ranges from 3.3% to 11.8%. Several associated factors of e-cigarette use were identified, including sociodemographic factors, traumatic childhood experience, peer and parental influence, knowledge and perception, substance use, and accessibility of e-cigarettes. These factors should be addressed though multifaceted interventions which simultaneously target multiple factors. Laws, policies, programs, and interventions must be strengthened and tailored to the needs of adolescents at risk of using e-cigarettes.