The Method and Arrangement for Predicting Engine Out Nitrogen Oxides (EONOx) includes training multiple candidate Artificial Neural Network (ANN) architectures using training data, and then selecting an ANN architecture from the candidates using an automated ANN architecture selection algorithm and testing data. An intelligent EONOx prediction or estimation system using the selected ANN architecture then provides an EONOx output variable, which is used along with the output of an EONOx sensor. The system is deployed into the engine controller. The training and testing sets of data include input variables from engine sensors and/or actuators that relate to EONOx, and may be acquired by testing a target engine. Selecting the optimal ANN architecture may be based on Root Mean Squared Error (RMSE) analysis using the automated ANN architecture algorithm and the training set of data.