This paper introduces a novel spectral collocation method for solving two-dimensional tempered space-fractional Zeldovich–Frank–Kamenetskii (ZFK) equations, which generalize the classical combustion model by incorporating tempered fractional diffusion operators. The tempered fractional ZFK equation is pivotal for modeling anomalous diffusion phenomena in thermal reaction and combustion systems, where nonlocal interactions and memory effects play a critical role. The proposed hybrid numerical scheme combines a spectral collocation method based on ultraspherical polynomials for spatial discretization with an implicit Runge–Kutta (IRK) technique for temporal integration. For the first time, we derive new tempered fractional differentiation matrices in physical space using ultraspherical polynomial bases, enabling efficient handling of the nonlocal tempered fractional operators. The results highlight the effectiveness of the new differentiation matrices in capturing anomalous diffusion phenomena while maintaining spectral accuracy, providing a robust framework for fractional combustion modeling.