In this work, we decipher the cation effect on the Au-catalyzed CO2 reduction reaction (CO2RR) as a model system to demonstrate that the key parameters in the MHC framework, i.e., the equivalent standard potential, reorganization energy, and vibronic coupling, can be expressed as functions of two experimentally accessible variables, i.e., the surface charge density and hydration free energy of cation. We show that the effect of different alkali metal and organic cations on CO2RR can be rationalized by a unified mechanistic framework. More importantly, the developed strategy and framework can be leveraged to elucidate the impact of the microenvironment on a broad range of PCET processes.