The modification of aluminum nanoparticles (Al NPs) by polyvinylidene fluoride (PVDF) can significantly enhance their reaction characteristics and reduce combustion agglomeration. However, the impact and underlying mechanisms of changes in interfacial binding methods between them on the reaction process remain unclear. In this study, the oxidation and combustion processes, as well as the agglomeration behavior of Al NPs under three different interfacial binding methods (mixing, with oxygenation layer coating, and without oxygenation layer coating) between Al NPs and PVDF were investigated by utilizing ReaxFF molecular dynamics simulations, density functional theory calculations, and ignition experiments. The results indicate that changes in the interfacial binding method significantly affect the oxidation behavior of Al NPs, and PVDF molecules exhibit different decomposition pathways on the surfaces of Al and Al2O3. During the combustion stage, different interfacial binding methods determine distinct reaction modes between Al NPs and PVDF. Based on these findings, a reaction mechanism for Al NPs and PVDF is proposed. This study addresses the gap in the field of the impact of interfacial binding methods on the reaction processes between Al NPs and PVDF, laying a theoretical foundation for future research and providing guidance for the practical application of Al-based modified fuels.