Catalytic processes are central to the goal of a sustainable future. A promising approach in developing catalytic materials is represented by the design of catalytic sites based on the knowledge of reaction mechanisms and structure-property relationships and aided by computation, and in the precise synthesis of these sites at the atomic and molecular level. The materials-pressure gap, however, still hinder the full realization of this strategy. Nanocrystal precursors, with tunable active sites and compositions, can help bridge this gap. The goal of this talk is to show how this approach can provide not only fundamental understanding of catalytic reactions, but also represent a way to precisely engineer catalytic sites to produce efficient catalysts that are active, stable and selective for several important catalytic transformations. Advances in the synthesis of these materials will be presented, in order to better understand the mechanism of colloidal nanocrystal formation and to control their structure and composition at the nanometer level. Examples of the use of these building blocks as supported systems or in combination with hybrid organic materials will be shown, both to understand trends in methane and CO2 activation, and in the preparation of optimized catalytic systems combining multiple active phases. In all these examples, important efforts to obtain precious structure-property relationships will be highlighted, with this knowledge used to prepare more efficient and stable catalysts for sustainable production of fuels and chemicals.