A flow-type apparatus and predictive framework were developed for measuring and estimating dipolarity/polarizability (π*) values of binary mixtures of supercritical carbon dioxide (scCO2)–cosolvents. The π* values of scCO2 with methanol and ethanol cosolvents (up to 10 mol %) are reported at the temperature ranging from 40 to 80 °C and pressure ranging from 10 to 20 MPa and were found to be dependent on fluid density. The predictive framework for scCO2–cosolvent mixtures proposed in this work was the modification by the addition of correction functions (g(ρCO2)) of local density enhancement into the previous predictive framework for binary liquid nonpolar–polar mixtures [Ind. Eng. Chem. Res. 2019, 58, 18986−18996]. Four g(ρCO2) forms with a function of CO2 density were evaluated by considering literature local density enhancements of pure CO2 obtained from (i) fluorescence, (ii) Raman, (ii) UV–vis spectroscopic techniques, and (iv) molecular dynamics simulations. The framework was applied to the prediction of π* of four scCO2–cosolvent mixtures (methanol, ethanol, 2-propanol, and 1,1,1,2-tetrafluoroethane (HFC134a)) and was found to give a reliable value with an overall relative deviation of 0.03 between the experimental and calculated data, where the fluorescence g(ρCO2) function provided a lower deviation than the other three functions. The application of the framework to separation processes showed that the π* values were found to explain the trends of solubility, extraction yield, and fractionation recovery. The π* values determined from the framework can be used to analyze solvent effect trends in many separation processes that required only cosolvent dipole moment, pure π* component, and CO2 density (pressure and temperature).