This study introduces a machine learning approach based on Artificial Neural Networks (ANNs) for the prediction of Marshall test results, stiffness modulus and air voids data of different bituminous mixtures for road pavements. A novel approach for an objective and semi-automatic identification of the optimal ANN’s structure, defined by the so-called hyperparameters, has been introduced and discussed. Mechanical and volumetric data were obtained by conducting laboratory tests on 320 Marshall specimens, and the results were used to train the neural network. The k-fold Cross Validation method has been used for partitioning the available data set, to obtain an unbiased evaluation of the model predictive error. The ANN’s hyperparameters have been optimized using the Bayesian optimization, that overcame efficiently the more costly trial-and-error procedure and automated the hyperparameters tuning. The proposed ANN model is characterized by a Pearson coefficient value of 0.868.