Drought stress as one of the most devastating abiotic stresses affects agricultural and horticultural productivity in many parts of the world. The application of melatonin can be considered as a promising approach for alleviating the negative impact of drought stress. Modeling of morphological responses to drought stress can be helpful to predict the optimal condition for improving plant productivity. The objective of the current study is modeling and predicting morphological responses (leaf length, number of leaves/plants, crown diameter, plant height, and internode length) of citrus to drought stress, based on four input variables including melatonin concentrations, days after applying treatments, citrus species, and level of drought stress, using different Artificial Neural Networks (ANNs) including Generalized Regression Neural Network (GRNN), Radial basis function (RBF), and Multilayer Perceptron (MLP). The results indicated a higher accuracy of GRNN as compared to RBF and MLP. The great accordance between the experimental and predicted data of morphological responses for both training and testing processes support the excellent efficiency of developed GRNN models. Also, GRNN was connected to Non-dominated Sorting Genetic Algorithm-II (NSGA-II) to optimize input variables for obtaining the best morphological responses. Generally, the validation experiment showed that ANN-NSGA-II can be considered as a promising and reliable computational tool for studying and predicting plant morphological and physiological responses to drought stress.