There is a dearth of data and evidence in the literature to assist the industry in determining the most appropriate strategies for large-scale deep retrofitting of non-domestic buildings to achieve healthy low-energy buildings. Support to decision-making and enabling deep retrofit of these buildings requires approaches such as long-term renovation strategies and building renovation passports. This paper compares the impact of single-step and staged retrofit approaches to improve the building energy performance of an existing building to a nearly zero-energy building (nZEB) level with improved comfort and optimal life-cycle costs. The novel developed methodological framework is applied to a university building built in 1975 (partially retrofit in 2005) that is expected to be completely retrofitted in 2020. A set of scenarios are analysed for the case study building using a combination of retrofit measures towards achieving the cost-optimal non-dominated solutions (Pareto front) based on multiple-objective optimisation for the decision-maker. The results highlight that a single-step retrofit can achieve a reduction of up to 60% in primary energy consumption and reduction of 38% in discomfort hours. The findings also indicate that nZEB performance with the primary energy consumption in the range of ~ 75-90 kWh m(-2) year(-1) (with plug loads) can be achieved cost-effectively through single-step deep retrofit for a university building. Results also highlighted the inability to achieve higher energy performance or improved comfort in two stages relative to completing a deep retrofit in a single stage. The results aim to contribute to the existing debate on the economic and environmental feasibility in realising long-term renovation strategies for existing non-domestic buildings, especially university buildings.