Commercial buildings are responsible for a significant share of the energy requirements of European Union countries. Related consumptions due to heating, cooling, and lighting appear, in most cases, very high and expensive. Since the real estate is renewed with a very small percentage each year and current trends suggest reusing the old structures, strategies for improving energy efficiency and sustainability should focus not only on new buildings, but also and especially on existing ones. Architectural renovation of existing buildings could provide an opportunity to enhance their energy efficiency, by working on the improvement of envelopes and energy supply systems. It has also to be noted that the measures aimed to improve the energy performance of buildings should pay particular attention to the cost-effectiveness of the interventions. In general, there is a lack of well-established methods for retrofitting, but if a case study achieves effective results, the adopted strategies and methodologies can be successfully replicated for similar kinds of buildings. In this paper, an iterative methodology for energy retrofit of commercial buildings is presented, together with a specific application on an existing office building. The case study is particularly significant as it is placed in an urban climatic context characterized by cold winters and hot summers; consequently, HVAC energy consumption is considerable throughout the year. The analysis and simulations of energy performance before and after the intervention, along with measured data on real energy performance, demonstrate the validity of the applied approach. The specifically developed design and refurbishment methodology, presented in this work, could be also assumed as a reference in similar operations.