To explore the impacts of various factors on the performance of concrete, the response surface methodology was adopted to optimize the concrete mix proportion. In the experiment, the water-binder ratio, the dosage of steel slag, and the content of desert sand were taken as variables, with a focus on analyzing the main performance indicators such as the slump of concrete, compressive strength, and splitting tensile strength. The experimental results indicate that the content of desert sand has the most significant influence on the slump of concrete, while the compressive strength and splitting tensile strength are mainly affected by the variation of the water-binder ratio. With the increase of the content of desert sand, the slump, compressive strength, and splitting tensile strength of concrete exhibit a trend of initially increasing and then decreasing. When the content of desert sand reaches 30%, the performance is optimal. The addition of steel slag can enhance the fluidity of desert sand concrete (DSC). As the amount of steel slag increases, the compressive strength of DSC shows a decreasing trend, and the tensile strength increases initially and then decreases. The addition of steel slag interacts with desert sand, particularly on the tensile strength of DSC. Through response analysis, the optimal mix proportion was obtained as a water-binder ratio of 0.39, a dosage of steel slag of 10%, and a content of desert sand of 30%, at which the comprehensive performance of DSC is the best. Finally, non-dominated sorting genetic algorithm Ⅱ（NSGA-Ⅱ) was utilized for multi-objective optimization, which yielded a more complete solution set, thereby providing certain technical support for the application of DSC.