In this work, spot-density gradient theory (DGT), with an approximate density profile in the vapor–liquid interfacial phase, was combined with ePC-soft-statistical associating fluid theory (SAFT) to describe the interfacial properties of binary mixtures. The developed model, which is termed as spot-DGT-ePC-SAFT, was first used for the mixtures containing common substances (e.g., alkane, benzene, CO2) to verify the model and compare the model performance with the rigorous DGT models. It shows that the surface tensions predicted with spot-DGT-ePC-SAFT are almost the same as those with the rigorous DGT, while spot-DGT costs much less calculation time. The developed spot-DGT-ePC-SAFT was further extended to ionic liquid (IL)–IL and IL–CO2 systems. Again, the predicted surface tensions agree well with the experimental data, indicating the reliability of the developed model for the IL-based systems.