We emphasize that the analytical method based on the MHC formalism outlined above does not depend on the specifics of CO2RR but is applicable to nonadiabatic PCET processes in general. The impact of microenvironment on a given PCET process could always be decomposed into contributions from 𝐸 * * , 𝐻 78 , 𝑆 C. and 𝜆 (Eq. S8). The difference in 𝑝𝐾 % between the proton donor and the conjugate acid of the proton acceptor dictates the effect of the microenvironment on the thermodynamics of the reaction (Eq. S7). For electrode-mediated PCETs, surface charge density is an effective and experimentally accessible descriptor with the Gauss' law, while the local electric field could be tuned by nearby functional groups and measured by the Stark shift of probe molecules in biological systems . Stationary perturbation theory could be employed to describe vibrational coupling (Eq. 8) as in the model system of Au-catalyzed CO2RR. The ability to attribute the impact of microenvironment on catalytic performance to several experimentally accessible variables will facilitate the design and optimization of broad range of catalytic systems in energy and biological fields.