Efficient pullulan production has long been a central research focus. This study used maltodextrin as the carbon source for pullulan production by Aureobasidium pullulans fermentation. A hybrid optimization approach, integrating orthogonal experimental design (OED), backpropagation artificial neural network (BP-ANN), and elite strategy non-dominated sequential genetic algorithm-II (NSGA-II), was developed. Range analysis based on OED revealed that MgSO4·7H2O significantly affects production but less impacts molecular weight, while pH notably influences molecular weight with a lesser effect on production, underscoring the need for multi-objective optimization. The BP-ANN model showed strong predictive capabilities, with goodness-of-fit values of 0.984 and 0.980 for production and molecular weight, respectively. Using this model as the fitness function for the optimization algorithm enhanced efficiency. Taking cost factors into account, the BP-ANN-NSGA-II algorithm identified the optimal fermentation medium conditions, resulting in a 6.89 % increase in production, a 368.97 % increase in molecular weight, and a 42.49 % reduction in cost. The maximum comprehensive optimization efficiency is 63.73 %, and the multi-objective optimization is better than the single objective optimization. This method significantly guides the improvement of pullulan fermentation optimization efficiency.