The shear strength prediction of concrete beams reinforced with FRP rebars and stirrups is one of the most complicated issues in structural engineering applications. Numerous experimental and theoretical studies have been conducted to establish a relationship between the shear capacity and the design variables. However, existing semi-empirical models fail to deliver precise predictions due to the intricate nature of shear mechanisms. To provide a more accurate and reliable model, machine learning (ML) techniques are adopted to study the shear behavior of concrete beams reinforced with FRP rebars and stirrups. A database consisting of 120 tested specimens is compiled from the reported literature. An artificial neural network (ANN) and a combination of ANN with a genetic optimization algorithm (GA-ANN) are implemented for the development of an ML model. Through neural interpretation diagrams (NID), the critical design factors, i.e., beam width and effective depth, shear span-to-depth ratio, compressive strength of concrete, FRP longitudinal reinforcement ratio, FRP shear reinforcement ratio, and elastic modulus of FRP longitudinal reinforcement rebars and FRP stirrups, are identified and determined as input parameters of the models. The accuracy of the proposed models has been verified by comparing the model predictions with the available test results. The application of the GA-ANN model provides better statistical results (mean value Vexp/Vpre equal to 0.99, R2 of 0.91, and RMSE of 22.6 kN) and outperforms CSA S806-12 predictions by improving the R2 value by 18.2% and the RMSE value by 52.5%. Furthermore, special attention is paid to the coupling effects of design parameters on shear capacity, which has not been reasonably considered in the models in the literature and available design guidelines. Finally, an ML-regression equation considering the coupling effects is developed based on the data-driven regression analysis method. The analytical results revealed that the prediction agrees with the test results with reasonable accuracy, and the model can be effectively applied in the prediction of shear capacity of concrete beams reinforced with FRP bars and stirrups.