The bimetallic 2D conductive MOFs of M1Pc-M2-O, possessing dual metal sites to realize flexible molecular-level structural modification, are brilliant catalysts for electrochemical CO2 reduction. However, the bimetallic centers bring about the complex regulatory mechanism of catalytic activity and obscure principles for catalyst design. Herein, systematical theoretical investigation unravels intrinsic descriptors to design favorable M1Pc-M2-O catalysts based on the discovered coarse-fine two-stage activity regulation mechanism. The reaction site controls the M-COOH distance of the key intermediate and therefore affects the reaction kinetics for the first stage of coarse regulation. The other metal site influents the d-band center of the reaction site and thus constitutes the second stage of fine regulation. The coarse and fine regulation are related to the valence electrons (V), electronegativity (E), and bond length (LM-N/O) between the metal and coordination atoms. The intrinsic descriptor ϕ = (4 × VM1 × (EM1 + EN/O)/EN/O + VM2 × (EM2 + EN/O)/EN/O) × LM1-N/O (with a coefficient ratio of 4 : 1) was eventually established and correlated well with the reported experiments. On this basis, the favorable catalysts CoPc-Zn-O and CoPc-Co-O were located. The research results could contribute to the diversity of bimetallic 2D c-MOFs in CO2RR.