Preferential solvation of pomalidomide (PMD) was explored in dimethyl sulfoxide (DMSO)-dimethylformamide (DMF), DMSO-tetrahydrofuran (THF), DMSO-methanol (MeOH), DMSO-isopropanol, DMSO-water, water-DMF, water-THF, water-MeOH, and water–isopropanol binary mixed solvents at 298.15 K. Bosch-Rose model was utilized to determine the electronic transition energies (ET) and other preferential solvation parameters, describing solute-solute and solute-solvent interactions. We found that λmax situation shifted with dielectric constant of the pure solvents meaningfully. According to the obtained results, ET enhanced and λmax shifted to the lower wavelengths as the percentage of DMSO decreased in the binary mixtures, remarking the important role of DMSO for stabilizing the excited state (π⁎) of PMD chromophore via efficient intermolecular solute-solvent interactions. In addition, the aqueous binary systems showed an optimum point for the ET values as the percentage of water changed in the solutions. The local mole fraction of the solvents in the cybotactic region was also estimated to describe the specific and non-specific interactions in the systems.