To study the effects of the fatigue performance due to the major design parameter of the orthotropic steel deck and to obtain a better design parameter, a construction parameter optimization method based on a backpropagation neural network (BPNN) and simulated annealing (SA) algorithm was proposed. First, the finite element (FE) model was established, and the numerical results were validated against available full-scale fatigue experimental data. Then, by calculating the influence surface of each fatigue detail, the most unfavorable loading position of each fatigue detail was obtained. After that, combined with the data from actual engineering applications, the weight coefficient of each fatigue detail was calculated by an analytic hierarchy process (AHP). Finally, to minimize the comprehensive stress amplitude, a BPNN and SA algorithm were used to optimize the construction parameters, and the optimization results for the conventional weight coefficients were compared with the construction parameters. It can be concluded that compared with the FE method through single-parameter optimization, the BPNN and SA method can synthetically optimize multiple parameters. In addition, compared with the common weighting coefficients, the weighting coefficients proposed in this paper can be better optimized for vulnerable parts. The optimized fatigue detail stress amplitude is minimized, and the optimization results are reliable. For these reasons, the parameter optimization method presented in this paper can be used for other similar applications.