In response to increasing concerns about climate change and resource depletion, improving building energy efficiency—particularly in heritage buildings—has become a critical focus. This study presents the energy audit of Palazzo Murena, a historic building that houses the University of Perugia’s administrative offices. The audit aimed to assess the building’s current energy performance and propose retrofit strategies compatible with its architectural constraints. Palazzo Murena features a complex heating system powered by district heating from a nearby thermal plant, distributed on vertical risers and a floor-by-floor ring network. The audit involved a comprehensive data collection process, including cadastral records, planning documents, energy certifications, consumption data, and technical building plans. Site inspections, structured checklists, and user questionnaires further informed the analysis. A detailed energy inventory and thermal load assessment for office spaces were developed. Experimental in-situ investigations validated envelope performance through thermal transmittance measurements, indoor environmental monitoring, and illuminance analysis. A dynamic energy model was developed using two years climate data, accounting for building envelope features, thermal bridges, and Heating, Ventilation and Air Conditioning (HVAC) zones. Several retrofit scenarios were evaluated, including standard upgrades, full-electric, and renewable-based solutions. Each solution was assessed for technical feasibility and economic impact, with the goal of reducing carbon dioxide emissions and enhancing energy performance, while preserving the building’s historic and artistic integrity. This case study demonstrates a scalable approach to sustainable retrofitting in heritage buildings.