The solution-mediated phase transformation process from cefaclor dihydrate to an ethanol-water solvate is analyzed by optical microscopy, powder X-ray diffraction, scanning electron microscopy and molecular modeling. The solution concentration and polymorphic composition during slurry transformation, as monitored using UV and Raman spectroscopy, respectively, reveal that the dihydrate transforms to the ethanol-water solvate at a low ethanol concentration in the mixture solvent. The transformation process is controlled by the growth of ethanol water solvate, which nucleates on the surfaces of the dihydrate crystals. Molecular simulation confirms the critical point of transformation between the dihydrate and the ethanol-water solvate, consistent with the experimental results. The results demonstrate the importance of the solvent composition and surface chemistry of dihydrate in promoting the heterogeneous nucleation of ethanol-water solvate and provide guidance for the process control for the target form of cefaclor required.