The overarching goal is to understand how to control selectivity through tuning cooperativity in multi-functional catalysts. We strive to understand the key descriptors that control selectivity as an indicator of catalytic performance, since selectivity opens a window into mechanistic pathways and higher selectivity means greater atom economy, better resource utilization, and higher energy efficiency. Specifically, we address the gap in understanding of how the properties of mixed oxides, both single phase catalysts (ABOx) and two-phased oxides, are related to catalytic performance. We hypothesize that by informed variation of the A and B cations in a mixed oxide ABOx, we can get cooperativity that leads to unique catalytic properties that are not achieved from the component oxide AOx or BOx and that in oxide supported catalysts the interface between the components provides a unique environment where cooperativity can lead to unique catalytic properties. It is the interactions and cooperation at the atomic level in these systems that are of interest, either between the sites on a crystallite surface or at the contact between phases. We start with precise synthesis to create catalysts that have a high level of structural and compositional definition to provide structure-catalytic relationships. We focus on catalytic reactions of oxygenated molecules, since the oxygen in the catalyst frequently enters into the intermediates in the reaction pathways and oxygenated molecules are the building blocks of many chemical processes. We probe the structure of the catalyst, their detailed surface chemistry and catalytic properties by a collection of state-of-the-art operando and in situ methods, including IR, Raman, and inelastic neutron scattering. We exploit methods that allow us to bridge the materials and pressure gaps between UHV and reactor based methods that together permit detailed kinetic and mechanistic understanding. Using single phase model crystalline surfaces and faceted nanoparticles we will consider questions of how reducibility and acid-base cooperativity on a mixed oxide catalyst work together to control selectivity in oxygenate reactions. We also utilize two-phase systems, core-shell and Janus particles, where cooperativity between the two phases and their interface control selectivity. Crosscutting these approaches to catalyst design is a focus on understanding the kinetics and mechanism of specific catalytic probe reactions that are selected to explore concepts in selectivity and reaction pathways.