The inaccuracy of resting energy expenditure (REE) prediction formulae to calculate energy metabolism in children may lead to either under- or overestimated real caloric needs with clinical consequences. The aim of this paper was to apply artificial neural networks algorithms (ANNs) to REE prediction. We enrolled 561 healthy children (2–17 years). Nutritional status was classified according to World Health Organization (WHO) criteria, and 113 were obese. REE was measured using indirect calorimetry and estimated with WHO, Harris–Benedict, Schofield, and Oxford formulae. The ANNs considered specific anthropometric data to model REE. The mean absolute error (mean ± SD) of the prediction was 95.8 ± 80.8 and was strongly correlated with REE values (R2 = 0.88). The performance of ANNs was higher in the subgroup of obese children (101 ± 91.8) with a lower grade of imprecision (5.4%). ANNs as a novel approach may give valuable information regarding energy requirements and weight management in children.