Abstract Palladium promotion and deposition on monoclinic zirconia are effective strategies to boost the performance of bulk In 2 O 3 in CO 2 -to-methanol and could unlock superior reactivity if well integrated into a single catalytic system. However, harnessing synergic effects of the individual components is crucial and very challenging as it requires precise control over their assembly. Herein, we present ternary Pd-In 2 O 3 -ZrO 2 catalysts prepared by flame spray pyrolysis (FSP) with remarkable methanol productivity and improved metal utilization, surpassing their binary counterparts. Unlike established impregnation and co-precipitation methods, FSP produces materials combining low-nuclearity palladium species associated with In 2 O 3 monolayers highly dispersed on the ZrO 2 carrier, whose surface partially transforms from a tetragonal into a monoclinic- like structure upon reaction. A pioneering protocol developed to quantify oxygen vacancies using in situ electron paramagnetic resonance spectroscopy reveals their enhanced generation because of this unique catalyst architecture, thereby rationalizing its high and sustained methanol productivity.