In this work, the modified attachment energy model was used to predict the crystal morphology of isosorbide mononitrate (ISMN) in the dichloromethane (CH₂Cl₂) solvent system and dichloromethane-n-hexane (CH₂Cl₂-C₆H₁₄) mixed solvent system. The solvent effect can significantly affect the crystal morphology, which can profoundly impact both the drug’s physicochemical properties and the subsequent technological treatment process. In addition, the interactions between solvent molecules and crystal faces were investigated using molecular dynamics simulation, and radial distribution function (RDF) analysis was performed to determine the types of interactions. The structural parameter S was introduced to characterize the roughness of each crystal surface; the change in the CH₂Cl₂ diffusion coefficient before and after the addition of C₆H₁₄ was analyzed using mean square displacement (MSD). The calculation results of the modified attachment energy from the two solvent systems revealed that C₆H₁₄ could accelerate crystal growth, while the crystal morphology was not greatly affected, which is of some significance as a guide for the industrial crystallization process.