This paper addresses the endemic problem of the gap between predicted and actual energy performance in public buildings. A system engineering approach is used to characterize energy performance factoring in building intrinsic properties, occupancy patterns, environmental conditions, as well as available control variables and their respective ranges. Due to the lack of historical data, a theoretical simulation model is considered. A semantic mapping process is proposed using principle component analysis (PCA) and multi regression analysis (MRA) to determine the governing (i.e., most sensitive) variables to reduce the energy gap with a (near) real-time capability. Further, an artificial neural network (ANN) is developed to learn the patterns of this semantic mapping, and is used as the cost function of a genetic algorithm (GA)-based optimization tool to generate optimized energy saving rules factoring in multiple objectives and constraints. Finally, a novel rule evaluation process is developed to evaluate the generated energy saving rules, their boundaries, and underpinning variables. The proposed solution has been tested on both a simulation platform and a pilot building-a care home in the Netherlands. Validation results suggest an average 25% energy reduction while meeting occupants' comfort conditions. Note to Practioners-This study presents a novel semantic rule generation process using GA and ANN with the objective to reduce the gap between predicted and actual energy consumption in public buildings. Due to the absence of historical energy consumption data, a theoretical simulation approach is used that takes into account a wide range of factors, including building fabric, occupancy patterns, and environmental conditions. Energy sensitive variables are then identified using PCA and MRA. These sensitive variables as well as available control variables (set points) are used to train an ANN to learn energy consumption patterns and behavior within the considered buildings. This trained network is then used as a cost function engine (predictor) for a GA-based optimization process to generate the optimized energy saving rules. Finally, a novel rule evaluation process is devised and implemented to assess energy saving rules quality and boundaries. All generated rules have been tested on both the proposed simulation environment and real buildings. Validation results suggest an average 25% energy reduction.