Abstract Buildings are responsible for some 40% of the total final energy consumption in the European Union and about 40% of the world’s primary energy consumption. Hence, the reduction of primary energy consumption is important for the overall energy chain. The scope of the current work is to assess the energy efficiency measures in the residential and small commercial sector and to develop a methodology and a software tool for their optimal prioritization. The criteria used for the prioritization of energy efficiency measures in this article are the primary energy consumption and the initial investment cost. The developed methodology used is generic and could be implemented in the case of a new building or retrofitting an existing building. A multi-objective mixed-integer non-linear problem (MINLP) needs to be solved and the weighted sum method is used. Moreover, the novelty of this work is that a software tool has been developed using ‘Matlab®’ which is generic, very simple and time efficient and can be used by a Decision Maker (DM). Two case studies have been developed, one for a new building and one for retrofitting an existing one, in two cities with different climate characteristics. The building was placed in Edinburgh in the UK and Athens in Greece and the analysis showed that the primary energy consumption and the initial investment cost are inversely proportional.