The ambitious European targets for decarbonizing the building sector by 2050 present significant challenges, particularly in the energy retrofitting of historical buildings. While conservative restoration approaches emphasize low-impact interventions on both the building envelope and mechanical systems, adapting historical buildings to contemporary functional requirements necessitates modernized system integration. This includes ensuring operational safety, precise indoor environmental control, and increased flexibility to meet updated thermal and energy performance standards by regulatory frameworks. The implementation of Building Automation and Control Systems (BACS) in historical buildings is becoming increasingly prevalent as a strategy to reduce energy consumption while simultaneously enhancing occupant comfort. To support effective design and planning, it is crucial to optimise BACS operational control, particularly in minimising a building’s operational energy demand. In this context, Model Predictive Control (MPC) has emerged as an advanced optimisation technique for enhancing energy efficiency in BACS. Unlike conventional rule-based or reactive control methods, MPC employs a predictive optimisation framework that anticipates future building conditions and dynamically adjusts control actions to minimise energy consumption while maintaining thermal comfort. This study evaluates the energy-saving potential of optimising BACS in a historical building located in southern Italy through various MPC strategies. Three control approaches were investigated: the integration of mechanical actuators on windows to enable automated natural ventilation, the dynamic reduction of the heating system’s supply temperature, and the optimisation of automatic shading management. The results demonstrate that implementing MPC-based BACS strategies can lead to energy consumption reductions of up to 20%, highlighting the potential of advanced control systems in enhancing the energy efficiency of historical buildings while preserving their architectural integrity.