In this study, interfacial tension (IFT) is measured between brine and crude oil (a sample of heavy oil from an Iranian oil reservoir) in the presence of two nonionic surfactants, KEPS 80 (Tween 80) and Behamid D, at different concentrations in order to optimize the concentrations of the surfactants. The surface response method is used to design the IFT measurement experiments. The experimental design and optimization is performed using the IFT as an objective function and temperature, concentration, and time as independent variables. In addition to the IFT measurement, various experiments such as stability tests of the surfactants in NaCl brine solutions, adsorption experiments on the carbonated rock surface, and phase behavior tests are performed to investigate the behavior of KEPS 80 and Behamid D in the enhanced oil recovery process. At the end, a model using the response surface statistical technique is designed for optimization of the concentrations of the surfactants, and a surfactant molecular migration mechanism is used for explanation of the dynamic IFT variation versus time. In the case of IFT experiments, the effect of surfactant concentration (at 1000, 3000, and 5000 ppm) on the dynamic IFT is investigated. The experiments are performed at four temperatures (25, 40, 50, and 67°C). The results show that the oil–brine IFT values can be reduced to about 4 mN m−1 in the presence of Behamid D and to about 1 mN m−1 in the presence of KEPS 80 at low concentrations.