Nigeria exhibits a heterogeneous culture and factors that can significantly impact the formation of public opinions toward implementing vaccination requirements, especially among the marginalized population. Examining the prevailing public sentiment and attitudes of the key population is crucial. The study employed a cross-sectional approach. Data was collected from HALG OSS sites in Cross River, Niger, and Lagos, focusing on HIV seropositive and non-HIV positive clients/program beneficiaries. 321 people were sampled, and the data was analysed descriptively using IBM-SPSS. The study findings reveals that social media is the primary information source (33.1%) and is significantly influenced by popular social media figures (35.0%). Support for vaccine mandates was high for arriving visitors (89.1%) and frontline healthcare workers (85.6%) but lower for other groups. Unvaccinated participants cited various reasons, such as time constraints (20.0%) and perceiving vaccination as a personal choice (20.0%). Encouragingly, 80.0% expressed a future intent to get vaccinated. Among unvaccinated individuals, 60.0% reported changed views on vaccination, with 80.0% considering side effects and vaccine effectiveness information persuasive. Participants trusted local media and the Ministry of Health but held low regard for government and opposition politicians. The majority supported measures like handwashing and improved social distancing to combat COVID-19. In Conclusion, Social media, led by popular personalities, significantly shapes COVID-19 vaccination perceptions among Nigeria’s key populations. Addressing concerns and using credible sources are essential for vaccine acceptance.