Vaccination is crucial for disease prevention, particularly in rural Nigeria, where access to healthcare is limited. This study examines the challenges to immunization programs, the impact of government policies and local health systems, and the effectiveness of control measures. Key challenges include logistical issues, such as inadequate health facilities, storage for vaccines, and equipment, as well as socio-cultural barriers like lack of knowledge, traditional beliefs, myths, and rumors. Government policies and health systems play a significant role in immunization efforts but are often hindered by resource shortages and inconsistent implementation. Effective strategies, such as mobile vaccination units, community health education, and integrating immunization with other health services, have shown promise in improving vaccination coverage. However, concerns about the sustainability of these interventions highlight the need for systemic strengthening, including community involvement and a reliable vaccine supply chain. This study emphasizes the importance of coordinated efforts by government, healthcare providers, and community leaders to address both structural and cultural barriers. Achieving 100% immunization coverage in rural areas requires inter-sectoral strategies that address social determinants of health. By tackling these underlying factors, sustainable improvements in immunization programs can be ensured, ultimately reducing the burden of vaccine-preventable diseases in hard-to-reach rural areas.