UiO-66, a Zr-based metal-organic framework (MOF), provides an ordered porous environment capable of adsorbing/retaining CO2 and oxygenated intermediates relevant for methanol synthesis. Although UiO-66-based composites containing Cu and Cu-Zn species show promising performance for CO2-to-methanol conversion, the role of the MOF framework in stabilizing the active metallic species under working conditions remains insufficiently understood. Here, the stabilization of copper species by UiO-66 and the influence of Zn promotion on Cu speciation and catalytic performance during CO2 hydrogenation are investigated. Operando X-ray absorption spectroscopy at the Cu, Zn, and Zr K-edges is combined with electron microscopy and density functional theory calculations to follow the evolution of metal species and the framework during reduction, reaction, and transient switching experiments. Zn promotes the formation and stability of highly dispersed Cu under reaction conditions, while the Zr6 nodes of UiO-66 respond dynamically through reversible hydroxylation and dehydroxylation. By correlating metal speciation, framework response, and methanol productivity under continuous-flow conditions, this work provides molecular-level insight into metal stabilization in Zr-based MOFs and informs the design of MOF based catalysts for CO2 hydrogenation.