Abstract This paper presents the integration of the evacuated tube solar collectors into a novel solar polygeneration plant. The analysis is performed by evaluating the energy and economic performance of the plant, coupled to a multi-effect distillation unit for seawater desalination, a single effect water lithium bromide absorption chiller, a biomass auxiliary heater, heat exchangers, tanks and balance-of-plant devices. Solar collectors produce heat, at about 90 °C, used for space heating and domestic hot water production, driving the absorption chiller (used for space cooling). Solar heat, combined the heat produced by the biomass auxiliary heater, also drives the multi-effect distillation unit producing desalinated water. The plant is simulated by means of a zero-dimensional dynamic model, developed in TRNSYS environment, which considers several control strategies, for the plant management. The economic analysis shows that the economic profitability significantly improves in case of feed-in tariffs, achieving a payback period of about 3.5 years. The optimization procedure performed by using the Design of Experiment method, returned a payback period of 2.4 years, by selecting the solar field area equal to 1200 m2, the tank dead band temperature to 2 °C, the summer/winter outlet set point temperature from the solar field equal to 95 °C/50 °C.