In this paper, a hierarchical multiscale model was presented to investigate the effect of thermal stress on the fracture toughness of nanoparticles/polymer nanocomposites. For these materials, zone shielding toughening mechanisms occurred at a region around the crack tip affect the fracture toughness. Among these mechanisms, the nanoparticle debonding from its surrounding material was considered in the current study. A representative volume element including a spherical nanoparticle, a pristine polymer phase, and an interphase material was postulated. The fracture toughness improvement due to debonding was obtained as a function of the constituents of the nanocomposites. The fracture toughness of polymer nanocomposites predicted by the multiscale model was compared with the experimental data. It was declared that temperature has a significant influence on the fracture toughness improvement induced by debonding mechanism. In addition, the impact of weight fraction of high-performance nanoparticles such as silica and alumina, and the interphase properties such as thermal expansion coefficient, thickness, and Young’s modulus on the fracture toughness was investigated. The achievement of this research can be employed to predict the fracture toughness of nanoparticles/polymer nanocompsoites utilized in many real-world applications such as adhesive, protective coatings for surfaces exposed to abrasion or corrosion, filters, food packaging, electrical insulation materials, and as the matrix of high-performance laminated composites widely used in aerospace and automotive industries.