In line with the decarbonization of the domestic sector to meet the 2050 climate neutrality targets, this paper describes the energy, economic, and environmental analysis of a set of different novel configurations of polygeneration installations to provide electricity, air conditioning, domestic hot water, and desalinated water for a building of 80 dwellings. All arrangements were designed to cover 100% of the five demands required in the building with renewable energy only, from photovoltaic (PV) and photovoltaic-thermal (PVT) panels and biomass backup boilers (BB). Electricity can be sold to or purchased from the grid without electrical storage with batteries. Additional electricity generation with thermoelectric generators (TEG) coupled to the PVTs, and the BB was explicitly analyzed. The choice of electrically or thermally activated technologies (heat pump, HP/single-effect absorption chiller, SEAC for cooling and multi-effect distillation, MED/reverse osmosis, RO for desalination) created four configurations from the basic structure based on solar and biomass sources. Thus, the paper has studied four designs in detail and applied them to three case studies corresponding to different locations in Spain. They were modeled with TRNSYS and included specific models for desalination technologies. Both structures provide important energy and CO2 savings concerning the conventional supply of the building demands. The novel life-cycle analysis approach further increases the lifetime CO2 savings for all configurations as well. The electric option (the combination of HP and RO for cooling and desalting) was, by far, the most attractive solution in terms of liability and lower investment required in the three case studies.