Introduction The global emergence of monkeypox has heightened public health concerns, particularly in regions with limited vaccine uptake. In Nigeria, understanding the factors influencing vaccination intentions is essential for developing effective public health strategies. Despite vaccine availability, hesitancy and varying degrees of acceptance persist, driven by factors such as self-efficacy, vaccine trust, and overall attitudes toward vaccination. Previous research highlights the importance of these factors in shaping health behaviors, particularly in vulnerable populations. In Benue State, where distinct health challenges affect key demographic groups such as people living with human immunodeficiency virus(PLHIV) and men who have sex with men (MSM), addressing vaccination intentions is critical for public health efforts. Objectives The objective was to assess the intention to receive the monkeypox vaccine, self-assessed knowledge levels, self-efficacy, and risk perception among the PLHIV, MSM, and the healthcare populationin Benue State, Nigeria. Additionally, the study aimed to evaluate public trust in vaccines and health authorities and to understand how these factors influence attitudes toward vaccination and overall perceptions of monkeypox-related health risks. Methodology A cross-sectional survey was conducted among 377 participants in Makurdi, Benue State, Nigeria, focusing onPLHIV, MSM, and healthcare workers. Participants were recruited using a snowball sampling technique, which leveraged social media platforms (WhatsApp, Facebook, and Telegram) and the Federal Medical Center in Makurdi. Data were collected using a structured questionnaire designed to assess self-efficacy, trust in vaccines, vaccination attitudes, and prior vaccination experiences. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY). Descriptive statistics were used to summarize the characteristics of the study population. Bivariate analyses, including chi-square tests and independent t-tests, were employed to explore the relationships between socio-demographic characteristics and vaccination intentions. Statistical significance was set at p < 0.05 for all analyses. Results The study revealed a significant positive relationship between self-efficacy and vaccination intention (p = 0.001). Trust in vaccinations and health authorities was also found to be a significant predictor of vaccination intention (p < 0.05). Furthermore, participants who had previously received the coronavirus disease 2019 (COVID-19) vaccine were more likely to express intention to receive the monkeypox vaccine (p = 0.000). However, the perception that the threat of monkeypox was exaggerated did not significantly impact vaccination intention (p = 0.4). Conclusion This study highlights the critical role of self-efficacy, trust in vaccines, and prior vaccination experiences in shaping the intention to receive the monkeypox vaccine in Benue State, Nigeria. The findings suggest that public health policies should prioritize enhancing trust in vaccines and health authorities, as well as boosting self-efficacy, to improve vaccination uptake. Addressing these factors may lead to more effective public health interventions against monkeypox and other infectious diseases.