Groundwater resources are required for domestic water supply, agriculture, and industry, and the strategic importance of water resources will only increase in the context of climate change and population growth. For optimal management of this crucial resource, exploration of the potential of groundwater is necessary. To this end, the objective of this study was the development of a new method based on remote sensing, deep neural networks (DNNs), and the optimization algorithms Adam, Flower Pollination Algorithm (FPA), Artificial Ecosystem-based Optimization (AEO), Pathfinder Algorithm (PFA), African Vultures Optimization Algorithm (AVOA), and Whale Optimization Algorithm (WOA) to predict groundwater potential in the North Central region of Vietnam. 95 springs or wells with 13 conditioning factors were used as input data to the machine learning model to find the statistical relationships between the presence and nonpresence of groundwater and the conditioning factors. Statistical indices, namely root mean square error (RMSE), area under curve (AUC), accuracy, kappa (K) and coefficient of determination (R²), were used to validate the models. The results indicated that all the proposed models were effective in predicting groundwater potential, with AUC values of more than 0.95. Among the proposed models, the DNN-AVOA model was more effective than the other models, with an AUC value of 0.97 and an RMSE of 0.22. This was followed by DNN-PFA (AUC=0.97, RMSE=0.22), DNN-FPA (AUC=0.97, RMSE=0.24), DNN-AEO (AUC=0.96, RMSE=0.25), DNN-Adam (AUC=0.97, RMSE=0.28), and DNN-WOA (AUC=0.95, RMSE=0.3). In addition, according to the groundwater potential map, about 25–30% of the region was in the high and very high potential groundwater zone; 5–10% was in the moderate zone, and 60–70% was low or very low. The results of this study can be used in the management of water resources in general and the location of appropriate wells in particular.