Fifth generation district heating and cooling systems are becoming increasingly popular due to their ability for working with low temperature of heat transfer fluids. Among the other benefits, this characteristic allows for a better exploitation of renewable energy sources. On the other hand, these networks require a fine design and precise management to exploit their full potential. Both these requirements can be met by using advanced simulation and optimisation tools. This research proposes a simulation tool purposely conceived for the design and the optimisation of fifth-generation district heating and cooling systems. This tool is capable of assessing the effects of each building-plant system on the whole district heating and cooling water loop, and to evaluate the effectiveness of diverse network morphology. These capabilities are due the level of detail of the mathematical modelling which takes into account the thermohydraulic characteristics of the network, each building thermo-physics properties, and the heat pump/chiller detailed operation. The described tool has been adopted to simulate an existing experimental network prototype (consisting of a central heat pump, behaving as thermal energy balancing station, and eight users), and the achieved results were compared to those experimentally obtained for validation aims. The capabilities of the validated tool have been demonstrated by investigating an innovative control logic (representing a further novelty of this research) for a “proof-of-concept” fifth-generation district heating and cooling network. In particular, by adopting a predictive control logic, the water loop temperature is dynamically optimised to minimise the entire network energy demand. The adopted control strategy has yielded significant primary energy savings, amounting to 10.3 MWh/year, with a rate of 6.5 % compared to the reference case characterised by a fixed network temperature. These results underscore the potential of the proposed method and demonstrate the effectiveness of the developed tool.