Energy loss has not been addressed effectively by policies introduced to encourage the preservation and enhancement of historical structures. Material and other constraints, together with safety standard improvements, do not always guarantee adequate levels of environmental performance. An optimization of retrofit measures to align with new uses, new standards of comfort, and energy saving are needed, as are studies based on new best practices for the enhancement of architectural heritage. This paper presents a method that uses dynamic models tared on non-destructive surveys, and based on compatible energy and structural interventions derived from preliminary analyses integrated into special design tools. Energy simulations were carried out using Design Builder (6.1.5.002, Designbuilder Software Ltd, Stroud, UK) software. The case study is a former hospital, S. Salvatore, in L’Aquila, an architecturally important building, severely damaged by an earthquake in 2009. The methodology presented in this research includes in-depth investigations coherently systematized into a multi-scenario output using simulation software. The results guarantee a high level of compatibility with restoration and seismic guidelines, and new building environmental performance requirements.