The study was conducted on the impact of thermophysical properties on eflornithine drug solute–solvent interactions in aqueous ethyl acetate and acetone at different concentrations and temperatures. The aim of this study is to enhance the understanding of eflornithine’s behavior in different solvents, which is crucial for its effective use in pharmaceutical applications. The density, molar volume, viscometric, and conductometric characteristics of the eflornithine drug solutions (0.025, 0.05, 0.075, 0.1, and 0.125 mol/kg) in acetone and 25% (v/v) aqueous ethyl acetate were measured within a temperature range of 298.15 K–318.15 K. Based on the determined density parameters, the following parameters were assessed: viscosity (η), equivalent molar conductance, limiting apparent molar volume (V0φ), apparent molar volume of transfer (V0φtr), and apparent molar volume (Vφ). The Masson empirical relationship and the viscosity-to-Jones-Dole (JD) equation were used to evaluate the partial molar volume (Vφ), experimental slope (SV), viscosity, and density data. Temperature and concentration were used to determine each parameter. For each set of dilutions, conductometric studies were conducted in both study solvents. The gathered data was analyzed in order to evaluate the ion–solvent interactions. The Walden product Λomηo’s positive temperature coefficient values indicate that the drug eflornithine functions as a structural modifier in acetone and aqueous acetyl acetate systems. The structure-making and breaking characteristics of the polar solvents acetone and ethyl acetate were identified.