Men who have sex with men (MSM) in Vietnam remain a key population disproportionately affected by HIV and emerging infections such as mpox. Despite the availability of prevention tools such as pre-exposure prophylaxis (PrEP) and digital health technologies, uptake remains low due to complex psychosocial and structural barriers. In this context, understanding behavioral, informational, and systemic factors influencing prevention readiness is essential to strengthen Vietnam’s public health response. This thesis aims to explore knowledge, perceptions, and access to HIV and mpox prevention among MSM in Vietnam. Using a multi-method approach, the research investigates the role of eHealth, behavioral predictors, stigma, and healthcare trust in shaping uptake and engagement with prevention strategies such as PrEP and vaccination. This thesis employed a multi-method research design, integrating systematic review, qualitative inquiry, and quantitative surveys to generate a comprehensive understanding of HIV and mpox prevention dynamics among MSM in Vietnam. Study I was a systematic review conducted following PRISMA guidelines, incorporating 54 eHealth interventions targeting HIV/STI prevention among MSM globally. These interventions were assessed using the ICROMS quality appraisal tool, with thematic synthesis used to analyze behavioral, psychosocial, and technological outcomes. Particular attention was paid to the duration, mode of delivery, and sustainability of behavior change effects. Studies II and III utilized qualitative focus group discussions (FGDs) in Hanoi, Vietnam. Study II explored eHealth preferences with 35 MSM across five stratified FGDs, while Study III examined PrEP acceptability, perceived barriers, and service design preferences among 30 HIV-negative or status-unknown MSM. The FGDs were transcribed, translated, and analyzed using directed content analysis to identify themes related to digital engagement, privacy, stigma, and trust. Studies IV and V were nationwide online cross-sectional surveys conducted between August and November 2022. Study IV involved 1,422 MSM and focused on awareness, access, and willingness to use PrEP. Study V involved 1,549 MSM and assessed mpox-related knowledge, misconceptions, and vaccine willingness. Participants were recruited using a snowball sampling strategy via trusted MSM community leaders. Surveys were administered anonymously using structured online questionnaires covering sociodemographic, behavioral, and psychosocial domains. Multivariable logistic and Tobit regression models were applied to identify predictors of prevention behavior and knowledge. The systematic review (Study I) synthesized 54 eHealth interventions for HIV/STI prevention among MSM globally. Most were randomized controlled trials conducted in high-income countries, predominantly web-based, and aimed at reducing sexual risk behaviors and increasing HIV/STI testing. About two-thirds employed behavioral theories, but methodological quality varied. The review highlighted that sustained behavior change remains a challenge, with limited long-term follow-up and a lack of booster interventions. Interventions integrating interactivity, personalization, and multi-platform access were associated with higher engagement and effectiveness. Qualitative studies (Study II and III) conducted in Hanoi provided contextual depth on MSM’s preferences for digital tools and perceptions of PrEP. MSM preferred smartphone-based, interactive, and discreet eHealth platforms, favoring private channels such as Facebook groups or encrypted chat over SMS, which was viewed as spam-like or privacy-threatening. Participants emphasized trust in content source, short and engaging formats, and integration with real-time services such as booking and counseling. Regarding PrEP, while participants acknowledged its value in reducing HIV risk and enhancing sexual agency, concerns about daily adherence, side effects, stigma, and cost were common. PrEP was seen as a complement—not a replacement—for condoms, and participants favored accessing PrEP through MSM-friendly CBOs or trusted clinics. Survey findings (Study IV and V) reinforced and extended these insights. Among 1,422 MSM across 62 provinces (Study IV), 56.1% were aware of PrEP, and 67.2% expressed willingness to use it. Willingness was higher among younger, better-educated MSM, those with higher income, and those open about their sexual orientation. However, recent experiences of sexual violence and stigma significantly reduced willingness, indicating psychological and structural barriers. Notably, inconsistent condom users and those engaging in group sex were more likely to express PrEP interest—suggesting risk-awareness as a motivating factor. In the context of emerging infections, Study V surveyed 1,549 MSM and found low mpox awareness despite high vaccine willingness (72.4%). Misconceptions about transmission were widespread, and only one in four participants knew where to get tested for mpox. Higher awareness was associated with youth, education, risk behaviors, and social support. Predictors of vaccine acceptance included general mpox knowledge, perceived necessity of vaccination, group sex engagement, and perceived HIV risk. These results emphasize the need for integrated communication strategies that align sexual health education with outbreak preparedness, particularly using trusted digital and peer-based channels. Together, the five studies revealed that while prevention interest among MSM in Vietnam is high—especially for PrEP and mpox vaccination—significant gaps in digital engagement, structural access, and trust must be addressed to translate willingness into action. This thesis provides an integrated understanding of HIV and emerging infectious disease prevention among MSM in Vietnam, drawing on findings from a systematic review, two qualitative studies, and two national surveys. Together, the studies highlight the readiness of MSM to engage with digital and biomedical prevention tools—such as eHealth platforms, PrEP, and vaccines—while also revealing substantial barriers related to stigma, disclosure, service trust, and knowledge gaps. The systematic review affirmed the short-term effectiveness of eHealth interventions when grounded in behavioral theory, but also pointed to limitations in long-term impact and sustainability. Qualitative findings showed that MSM valued credible, interactive, and private online interventions, yet remained concerned about information overload and inadvertent disclosure. Surveys confirmed a high willingness to use PrEP and accept mpox vaccination but revealed low awareness and structural obstacles to access. Psychosocial factors such as stigma, mental health distress, and sexual violence were consistently associated with lower prevention engagement. To close the gap between willingness and action, future health programs must prioritize integrated, stigma-free, and community-centered service models. This thesis offers key recommendations for designing inclusive digital and biomedical interventions, improving policy, and ensuring that MSM in Vietnam are equitably reached by national HIV and infectious disease prevention strategies.