In this paper, an optimization approach was presented for the flexural strength and stiffness design of reinforced concrete beams. Surrogate modeling based on machine learning was applied to predict the responses of the structural system in three-point flexure tests. Three design input variables, the area of steel bars in the compression zone, the area of steel bars in the tension zone, and the area of steel bars in the shear zone, were adopted for the dataset and arranged by the Box-Behnken design method. The dataset was composed of thirteen specimens of reinforced concrete beams. The specimens were tested under three-points flexure loading at the age of 28 days and both the failure load and the maximum deflection values were recorded. Compression and tension tests were conducted to obtain the concrete data for the analysis and numerical modeling. Afterward, finite element modeling was performed for all the specimens using the ATENA program to verify the experimental tests. Subsequently, the surrogate models for the flexural strength and the stiffness were constructed. Finally, optimization was conducted supporting on the factorial method for the predicted responses. The adopted approach proved to be an excellent tool to optimize the design of reinforced concrete beams for flexure and stiffness. In addition, experimental and numerical results were in very good agreement in terms of both the failure type and the cracking pattern. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.