Abstract Multimodal measurements involving time‐resolved Ni and Cu K edges Quick‐EXAFS, time‐resolved hyperspectral Full Field Quick‐EXAFS imaging with micrometer spatial resolution and aberration‐corrected Environmental Scanning Transmission Electron Microscopy have been performed over a NiCu catalyst used for the ethanol steam reforming reaction to establish structure‐activity relationships after regeneration. Activated catalysts are composed of 5–10 nm monometallic nickel nanoparticles and larger bimetallic randomly alloyed NiCu nanoparticles (NPs). After 3 h time on reactive stream, the monitoring of the regeneration of the coked deactivated catalyst at 500 °C by Full Field hyperspectral XAS imaging evidences that the oxidative propagation front affects faster metallic Ni species than metallic Cu ones as a result of the stronger oxophilic character of the former compared to the latter. Furthermore, ESTEM characterization of the deactivated catalyst when passing from H 2 to O 2 atmosphere at 500 °C for burning coke deposits evidences the fragmentation of the Ni and NiCu‐NPs driven by the Kirkendall effect in the encapsulated coked catalyst. The resulting increase of specific surface of active species is assumed to be responsible for the activity boost observed after regeneration.