This paper proposes a solution to enhance and compare different neural network (NN)-based side-slip angle estimators. The feed-forward neural networks (FFNNs), recurrent neural networks, long short-term memory units (LSTMs), and gated recurrent units are investigated. However, there is a lack in the selection criteria of the architectures’ hyper-parameters. Therefore, the genetic algorithm is integrated with the NN-based estimators to find the optimal hyper-parameters for the studied architectures. The tuned hyper-parameters in this work include the number of neurons, number of layers, activation function, optimizer type, and learning rate. The objective function of the optimization problem is minimizing the root-mean-square error (RMSE) on multiple testing data. The optimal models are further included in the design of a hybrid NN estimator with Kalman filter. In the hybrid estimators, the optimal NN estimators are used as virtual sensors to correct the prediction of the side-slip angle resulting from the mathematical lateral vehicle model. Eventually, the performance of the best selected model is evaluated in terms of different metrics; mean RMSE, mean error variance, mean training time, and mean estimation time. LSTMs are found to achieve the lowest mean RMSE while being tested on highly generalized data yielding the highest training and estimation time. However, FFNNs achieve the lowest RMSE while being tested on low generalized data and the lowest training and estimation time. Meanwhile, it is observed that the hybrid estimators achieved lower RMSE with great enhancement compared to the non-hybridized ones proving the effectiveness of the proposed approach and increasing the side-slip estimation generalization ability in unknown environments with high uncertainties, which are not covered by the training dataset for the NNs estimators.