In this study, an inverse method with the integration of finite element simulation and optimization algorithms is proposed to determine the flow curve of cylindrical specimen characterized by the modified Voce hardening model. The tensile test is repetitiously simulated with different combinations of model parameters designed through Latin hypercube design method, where the baseline values and variation ranges of model parameters are identified through Leroy–Bridgman method, obtaining different simulated load–displacement curves. The corresponding response is defined as the sum of the absolute area difference between the simulated load–displacement curves and the experimental one. The relationship between the model parameters and the response is established through response surface methodology and the optimal parameters combination in the modified Voce model is then determined through nonlinear programming by quadratic Lagrangian. In the case of uniaxial tensile test of mild steel Q345, the inversely identified flow curve is validated by numerically reproducing the experimental load–displacement curve and necking profile. The results indicate that the proposed inverse method is capable of evaluating the flow curve in large range of strains for cylindrical specimen accurately.