Abstract: This study explores the adsorption and reaction of methanol on the CeO₂(111) and Ni/CeO₂(111) surfaces, highlighting the essential role of metal-support interaction in methanol decomposition by a synergistic approach encompassing synchrotron radiation photoemission spectroscopy, X-ray photoelectron spectroscopy, infrared reflection and absorption spectroscopy, and temperature-programmed desorption. Our findings reveal that Ni deposited on the CeO₂(111) surface, followed by annealing to 700 K, leads to the formation of Ce-O-Ni mixed oxide as the dominant phase. The Ni²⁺ species facilitate the methoxy decomposition into CO and H₂ within 300–430 K, with a small amount of formaldehyde also forming at the edge sites of ceria. Additionally, some methoxy adsorbed on the bare CeO₂ surface migrates to the Ce-O-Ni mixed oxide, where they decompose into CO and H₂ at 500–600 K, accompanied by a portion of the methoxy interacting with ceria to generate formaldehyde. Upon exposure to methanol at 500 K, the Ni²⁺ species are reduced to metallic Ni⁰, alongside the formation of coke and Ni₃C, ultimately resulting in catalyst deactivation. However, reintroducing O₂ reactivates these sites by oxidizing metallic Ni⁰ and Ni₃C species. This study highlights the pivotal role of metal-support interaction in promoting oxygen transfer from ceria to Ni, thereby enhancing methoxy decomposition and significantly improving the performance of Ni-based catalysts for methanol decomposition into CO and H₂.