WaterWater and energyEnergy areProcess integration two categories of resourcesResource which are fundamental for all human activities in general. In the context of end-use sectors, these are in general present in all sites (for instance, in the case of process industry, all plants possess a determinate number of waterWater-using and energy-using processes). The research on all potential interdependencies possible to be established between waterWater and energyEnergy resourcesResource, as encompassed by the concept of waterWater-energy nexus-energy nexusWater-energy nexus, is relevant for the understanding of the improvement of the use of both these resourcesResource. A commonly implemented concept for the assessment and performance of the improvement of the use of several categories of resourcesResource in a determinate site has been process integrationProcess integration. Similarly to the concept of water-energy nexusWater-energy nexus, it deals with potential interdependencies between several resourcesResource, in this case with all potential interconnections between existing processes established by material and energy stream recirculation. The application of process integrationProcess integration principles to the case of the improvement of water and energyEnergy resource use in a simultaneous manner is thus significant of the promotion of the water-energy nexusWater-energy nexus character of a determinate site. In this chapter, it is performed and exploitation of the role of process integrationProcess integration in the context of the water-energy nexusWater-energy nexus, by exploiting several existing methodologies, with a particular focus being given to innovative paradigm of Water and EnergyEnergy Integration SystemsWater and Energy Integration Systems (WEIS) and its digital twinDigital twin-based counterpart, designated as ThermWatt.