The one-pot CO2 hydrogenation to lower olefins involves the integration of two catalytic reactions in a single reactor: the conversion of CO2 into methanol (CTM) and its subsequent conversion into lower olefins (MTO). This approach requires two catalysts cooperating in the same reactor, posing different challenges in terms of synergies and interactions between the two active phases. In this work, we investigate the effect of process conditions and arrangements between In2O3-ZrO2 (CTM catalyst) and SAPO-34 (MTO catalyst) on the lower olefins yield. We show that the distance between CTM and MTO active sites, studied by assessing different catalyst arrangements spanning from an intimate mixture obtained through mortar mixing to a complete segregation of the catalysts (i.e., consecutive beds), plays a key role in driving the products distribution. However, the thermodynamic equilibrium of the reverse water gas shift limits CO2 conversion in the investigated conditions. Finally, we discuss the stability of the catalytic performances: the characterization of the spent samples after ∼400 h on stream indicated the deactivation of the catalytic materials in all investigated cases, with In sintering on the methanol catalyst, and SAPO-34 losing both P and Al due to hydrothermal aging; indications of In migration on SAPO-34 were also observed when the two catalyst are in contact.