It is of great importance to establish a quantitative structure property relationship model that can correlate the separation performance of MOFs to their physicochemical features. In complement to the existing studies that screened the separation performance of MOFs from the adsorption selectivity calculated at infinite dilution, this work aims to build a QSPR model that can account for the CO2/N-2 mixture (15:85) selectivity of an extended series of MOFs with a very large chemical and topological diversity under industrial pressure condition. It was highlighted that the selectivity for this mixture under such conditions is dominated by the interplay of the difference of the isosteric heats of adsorption between the two gases and the porosity of the MOF adsorbents. On the basis of the interplay map of both factors that impact the adsorption selectivity, strategies were proposed to efficiently enhance the separation selectivity of MOFs for CO2 capture from flue gas. As a typical illustration, it thus leads us to tune a new MOF with outstanding separation performance that will orientate the synthesis effort to be deployed.