The direct hydrogenation of CO2 to methanol offers the potential to convert a major greenhouse gas into a useful energy carrier, yet its industrial implementation is hampered by the limited stability and selectivity of the traditionally employed Cu-based catalysts. Reducible metal oxides, for instance indium oxide, have shown promising catalytic performance for the hydrogenation of CO2 to methanol. However, their active sites, the prevailing reaction pathways, and the deactivation mechanisms are understudied so far. Here, we will use systematically modified indium oxide nanoparticles (via structural doping) as well-defined materials to gain atomic level understanding of the functioning catalyst at different stages (active and deactivated).