Vaccine acceptance is a crucial component of a viable immunization program in healthcare system, yet the disparities in new and existing vaccination adoption rates prevail across regions. Disparities in the rate of vaccine acceptance result in low immunization coverage and slow uptake of newly introduced vaccines. This research presents an innovative AI-driven predictive model, designed to accurately forecast vaccine acceptance within immunization programs, while providing high interpretability. Primarily, the contribution of this study is to classify vaccine acceptability into Low, Medium, Partial High, and High categories. Secondly, this study implements the Feature Importance method to make the model highly interpretable for healthcare providers. Thirdly, our findings highlight the impact of demographic and socio-demographic factors on vaccine acceptance, providing valuable insights for policymakers to improve immunization rates. A sample dataset containing 7150 data records with 31 demographic and socioeconomic attributes from PDHS (2017–2018) is used in this paper. Using the LightGBM algorithm, the proposed model constructed on the basis of different machine-learning procedures achieved 98% accuracy to accurately predict the acceptability of vaccines included in the immunization program. The association rules suggest that higher SES, region, parents’ occupation, and mother’s education have an association with vaccine acceptability.