A major concern in assessing the structural condition of existing flexible pavements is the estimation of the mechanical properties of constituent layers, which is useful for the design and decision-making process in road management systems. This parameter identification problem is truly complex due to the large number of variables involved in pavement behavior. To this end, non-conventional adaptive or approximate solutions via Artificial Neural Networks – ANNs – are considered to properly map pavement response field measurements. Previous investigations have demonstrated the exceptional ability of ANNs in layer moduli estimation from non-destructive deflection tests, but most of the reported cases were developed using synthetic deflection data or hypothetical pavement systems. This paper presents further attempts to back-calculate layer moduli via ANN modeling, using a database gathered from field tests performed on three- and four-layer pavement systems. Traditional layer structuring and pavements with a stabilized subbase were considered. A three-stage methodology is developed in this study to design and validate an “optimum” ANN-based model, i.e., the best architecture possible along with adequate learning rules. An assessment of the resulting ANN model demonstrates its forecasting capabilities and efficiency in solving a complex parameter identification problem concerning pavements.