The excess of the chemical fertilizers not only causes the environmental pollution but also has many deteriorating effects including global warming and alteration of soil microbial diversity. In conventional researches, chemical fertilizers and their concentrations are selected based on the knowledge of experts involved in the projects, which this kind of models are usually subjective. Therefore, the present study aimed to introduce the optimal concentrations of three macro elements including nitrogen (0, 100, and 200 g), potassium (0, 100, 200, and 300 g), and magnesium (0, 50, and 100 g) on fruit yield (FY), fruit length (FL), and number of rows per spike (NRPS) of greenhouse banana using analysis of variance (ANOVA) followed by post hoc LSD test and two well-known artificial neural networks (ANNs) including multilayer perceptron (MLP) and generalized regression neural network (GRNN). According to the results of ANOVA, the highest mean value of the FY was obtained with 200 g of N, 300 g of K, and 50 g of Mg. Based on the results of the present study, the both ANNs models had high predictive accuracy (R2 = 0.66–0.99) in the both training and testing data for the FY, FL, and NRPS. However, the GRNN model had better performance than MLP model for modeling and predicting the three characters of greenhouse banana. Therefore, genetic algorithm (GA) was subjected to the GRNN model in order to find the optimal amounts of N, K, and Mg for achieving the high amounts of the FY, FL, and NRPS. The GRNN-GA hybrid model confirmed that high yield of the plant could be achieved by reducing chemical fertilizers including nitrogen, potassium, and magnesium by 65, 44, and 62%, respectively, in compared to traditional method.