Complex microscopic simulation models of strategic Air Traffic Management (ATM) performance assessment and decision-making are hindered by several factors. One of the most important is the existence of hidden parameters—such as aircraft take-off weight (TOW) and the selected cost index (CI)—which, if known, would allow for more effective performance modeling methodologies for assessing Key Performance Indicators (KPIs) at various levels of abstraction/detail, e.g., system-wide, or at the level of individual flights. This research proposes a data-driven methodology for the estimation of flights’ hidden parameters combining mechanistic and advanced Artificial Intelligence/Machine Learning (AI/ML) models. Aiming at microsimulation models, our goal is to study the effect of these estimations on the prediction of flights’ KPIs. In so doing, we propose a novel methodology according to which data-driven methods are trained given optimal trajectories (produced by mechanistic models) corresponding to known hidden parameter values, with the aim of predicting hidden parameters’ values of unseen trajectories. The results show that estimations of hidden parameters support the accurate prediction of KPIs regarding the efficiency of flights: fuel consumption, gate-to-gate time and distance flown.