AbstractThe understanding of catalyst active sites is a fundamental challenge for the future rational design of optimized and bespoke catalysts. For instance, the partial reduction of Ce⁴⁺ surface sites to Ce³⁺ and the formation of oxygen vacancies are critical for CO₂ hydrogenation, CO oxidation, and the water gas shift reaction. Furthermore, metal nanoparticles, the reducible support, and metal support interactions are prone to evolve under reaction conditions; therefore a catalyst structure must be characterized under operando conditions to identify active states and deduce structure‐activity relationships. In the present work, temperature‐induced morphological and chemical changes in Ni nanoparticle‐decorated mesoporous CeO₂ by means of in situ quantitative multimode electron tomography and in situ heating electron energy loss spectroscopy, respectively, are investigated. Moreover, operando electron energy loss spectroscopy is employed using a windowed gas cell and reveals the role of Ni‐induced hydrogen spillover on active Ce³⁺ site formation and enhancement of the overall catalytic performance.