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This study investigates the electronic and structural properties of heterojunctions formed by mono-/bi-layers of graphene on a cerium oxide (CeO2) substrate. By utilizing first-principles calculations, we analyze the effects of the CeO2 substrate on graphene’s electronic structure and interfacial properties. The presence of the CeO2 substrate induces significant modifications in the band structure, including the formation of interface states and changes in the bandgap. The interfacial bonding and lattice matching play crucial roles in determining the heterojunction’s electronic behavior. Furthermore, we examine the charge transfer phenomena and its influence on electrical conductivity and carrier mobility. This research provides insights into the design and optimization of graphene-based devices on CeO2 substrates for potential electronic and optoelectronic applications.