Electrification is a key priority of the European Union, focusing on saving energy resources and mitigating carbon emissions through enhancing restrictions on relative policies and initiatives. For such goals to be achieved, investing in renewable energy technologies on large- and small-scale projects is promoted. These efforts were implemented in the building sector too, highlighting the importance of optimal decisions in improving the energy performance of buildings, from an economic, energy and environmental perspective. In this context, this paper aims to elaborate a decision-making methodology for building thermal design, considering the optimal selection and operation of multi-energy systems focused on renewable technologies. Solar thermal collectors, photovoltaic systems and heat pumps were included in an Energy Hub for meeting the heating, cooling and domestic hot water energy demand. Optimal decisions were achieved by formulating Mathematical Programming models in GAMS, for minimizing economic, energy and environmental parameters of the systems under a life cycle perspective. The proposed methodology was implemented in a residential building case study. Results show that combining heat pumps with photovoltaics is preferable for all of the examined criteria, while a sensitivity analysis of the economic, energy and environmental parameters, influencing the energy mixture, leads to optimal solutions with the participation of different energy systems.