The growing development of technologies and processes for resource treatment and recovery is offering endless possibilities for creating new plant-wide configurations or modifying existing ones. However, the configurations’ complexity, the interrelation between technologies and the influent characteristics turn decision-making into a complex or unobvious process. In this frame, the Plant-Wide Modelling (PWM) library presented in this paper allows a thorough, comprehensive and refined analysis of different plant configurations that are basic aspects in decision-making from an energy and resource recovery perspective. In order to demonstrate the potential of the library and the need to run simulation analyses, this paper carries out a comparative analysis of WWTPs, from a techno-economic point of view. The selected layouts were (1) a conventional WWTP based on a modified version of the Benchmark Simulation Model No. 2, (2) an upgraded or retrofitted WWTP, and (3) a new Wastewater Resource Recovery Facilities (WRRF) concept denominated as C/N/P decoupling WWTP. The study was based on a preliminary analysis of the organic matter and nutrient energy use and recovery options, a comprehensive mass and energy flux distribution analysis in each configuration in order to compare and identify areas for improvement, and a cost analysis of each plant for different influent COD/TN/TP ratios. Analysing the plants from a standpoint of resources and energy utilization, a low utilization of the energy content of the components could be observed in all configurations. In the conventional plant, the COD used to produce biogas was around 29%, the upgraded plant was around 36%, and 34% in the C/N/P decoupling WWTP. With regard to the self-sufficiency of plants, achieving self-sufficiency was not possible in the conventional plant, in the upgraded plant it depended on the influent C/N ratio, and in the C/N/P decoupling WWTP layout self-sufficiency was feasible for almost all influents, especially at high COD concentrations. The plant layouts proposed in this paper are just a sample of the possibilities offered by current technologies. Even so, the library presented here is generic and can be used to construct any other plant layout, provided that a model is available.