Membrane desalination (MD) is an efficient process for desalinating saltwater, combining the uniqueness of both thermal and separation distillation configurations. In this context, the optimization strategies and sizing methodologies are developed from the balance of the system’s energy demand. Therefore, robust prediction modeling of the thermodynamic behavior and freshwater production is crucial for the optimal design of MD systems. This study presents a new advanced machine-learning model to obtain the permeate flux of a tubular direct contact membrane distillation unit. The model was established by optimizing a long-short-term memory (LSTM) model by an election-based optimization algorithm (EBOA). The model inputs were the temperatures of permeate and the feed flow, and the rate and salinity of the feed flow. The optimized model was compared with other optimized LSTM models by sine–cosine optimization algorithm (SCA), artificial ecosystem optimizer (AEO), and grey wolf optimization algorithm (GWO). All models were trained, tested, and evaluated using different accuracy measures. LSTM-EBOA outperformed other models in predicting the permeate flux based on different accuracy measures. LSTM-EBOA had the highest coefficient of determination of 0.998 and 0.988 and the lowest root mean square error of 1.272 and 4.180 for training and test, respectively. It can be recommended that this paper provide a useful pathway for sizing parameters selection and predicting the performance of MD systems that makes an optimally designed model for predicting the freshwater production rates without costly experiments.