Preferential solvation of pomalidomide (PD) was explored in the binary mixtures of water, ethanol, ethylene glycol (EG), and propylene carbonate (PC) biocompatible solvents. The experiments were carried out using the standard protocols of homogenized solutions preparation at 298.15 K. Bosch–Rosés model, which has been extensively utilized for studying the binary solvents, was utilized to find the electronic transition energies, ET, and other preferential solvation parameters, describing solute-solvent and solute-solute interactions. Shifting λmax values respect to the dielectric constants of the pure solvents was carefully monitored and the results indicated that PD had lowest λmax in water and PC among HBD and HBA solvents, respectively. According to ET results, DMSO-EG binary solvent stabilized the ground state of the drug chromophore group while the rest of binary solvents stabilized its first excited state much effectively and this was due to the preferential solvation phenomenon. The results indicated that the probe molecules preferred to be solvated by DMSO rather than other solvents in the binary mixtures of DMSO-H2O, DMSO-PC, and DMSO-Ethanol, meaning that the presence of DMSO in the cybotactic region is mostly preferred. About DMSO-EG system, however, the situation was different and EG was preferred rather than DMSO. The abundance of pure solvents and/or complex solvent molecules in the cybotactic region around the solute was discussed based on the local mole fractions, kindly demonstrating specific and non-specific interactions between the solute and solvent molecules.