Abstract Background Despite the continuing decline of HIV/AIDS incidence and prevalence in the general population of Vietnam, HIV rates remains high in three key subpopulations: injecting drug users (IDUs), men who have sex with men (MSM) and female sex workers (FSWs). This study aims to identify the common sociodemographic characteristics and behavioural risk factors among three key populations for HIV infection in Vietnam. Methods This study used a systematic review and meta-analysis to synthesise findings from published studies on HIV prevalence and associated risk factors among the three at-risk groups. Five electronic databases were used to identify peer-reviewed articles in relevant topics. Comprehensive Meta-Analysis software was used to estimate pooled prevalence in the combined study population and to determine the effect sizes of the common risk factors on HIV outcome. Results Of the 18 included studies, 6 focused on IDUs, 8 on FSWs and 4 on MSM, accounting for a total of 16,304 participants. The overall prevalence of HIV among the three at-risk groups based on meta-analysis was 11.8% (95%CI: 0.072-0.188). The identified common risk behaviours for HIV infection included injecting drug use (OR: 21.3, 95%CI: 6.5-69.3), sharing injecting equipment (OR: 4.2, 95%CI: 2.1-8.2) and inconsistent condom use (OR: 2.6, 95%CI: 1.5-4.4). The associated socio-demographic characteristics with HIV (+) included young age, single/ unmarried, low education and income. Conclusions/Key messages The findings of this study suggested that injecting drug use may can contribute to developing more affective prevention measures targeting these high-risk groups and reducing the risk of HIV transmission to the general population.