Decarbonization targets and global political instabilities push the European Commission to elaborate strategies to ensure more affordable and secure energy. Within these strategies, e.g., RePowerEU, Power to Gas (P2G) is foreseen to become a key play for the successful transition towards a sustainable energy system. A rigorous methodology to investigate P2G plants’ potential and optimize the techno-economic performances is therefore essential for an effective scale up and implementation of P2G plants. Therefore, this study aims to show how energy modelling tools can be used to support decision-makers to identify potential locations of P2G plants and furthermore estimate the techno-economic performance of the plants. In this study, three energy modelling tools were developed and adapted to investigate the P2G design and planning at different levels of detail in the Apulia region (Italy), considering the integration with the energy system in order to ensure a complete assessment.