In the transition to a more circular economy, better catalysts are urgently needed for the hydrogenation of CO2 to methanol and dimethyl ether. Herein we aim to reveal the synergetic interaction between neighbouring Zn atoms on a defective alumina support (Al2O3-x), which greatly enhanced the CO2 to DME catalytic activity and reduced the activation energy relative to isolated atoms. Employing operando XAS, we propose to study how Zn atom density on the support influences the Zn coordination environments and electronic properties at different reaction temperatures and pressures, and to verify the synergistic activation pathways of CO2 over neighbouring Zn single atoms, as anticipated from our previous kinetic studies. Combining experimental results and theoretical calculations, we expect to reveal the fundamental influence of the spatial distribution of metal atoms on the reaction pathways and activation energies, to guide rational design of practical and efficient industrial catalysts.