Hyperparameter tuning is an important process to maximize the performance of any neural network model. This present study proposed the factorial design of experiment for screening and response surface methodology to optimize the hyperparameter of two artificial neural network algorithms. Feed-forward neural network (FFNN) and radial basis function neural network (RBFNN) are applied to predict the permeate flux of palm oil mill effluent. Permeate pump and transmembrane pressure of the submerge membrane bioreactor system are the input variables. Six hyperparameters of the FFNN model including four numerical factors (neuron numbers, learning rate, momentum, and epoch numbers) and two categorical factors (training and activation function) are used in hyperparameter optimization. RBFNN includes two numerical factors such as a number of neurons and spreads. The conventional method (one-variable-at-a-time) is compared in terms of optimization processing time and the accuracy of the model. The result indicates that the optimal hyperparameters obtained by the proposed approach produce good accuracy with a smaller generalization error. The simulation results show an improvement of more than 65% of training performance, with less repetition and processing time. This proposed methodology can be utilized for any type of neural network application to find the optimum levels of different parameters.