A carbon-neutral energy system is the cornerstone of a decarbonised economy in line with the 2015 Paris Agreement. According to the literature, high-quality renewable energy sources (RES) in combination with increased energy efficiency, storage, sector coupling, demand-side management and digitalisation can be said to provide good prospects for a low carbon supply of electricity, heat and fuels for households, transport and industry. While most studies focus on the EU or national levels, policies are ultimately implemented at regional and local levels. This chapter provides an overview of key elements of viable energy decarbonisation pathways, while paying attention to the policy goals and context of the study area, presents preliminary findings on regional RES potentials and proposes two different models for modelling the energy system in the Upper Rhine Region (TMO). PERSEUS-EU aims to find the most cost-efficient pathways to reach EU policy goals integrating regional RES, while the Regional Energy Planning Model (REPM) analyses regional decarbonisation scenarios assessing the required energy storage and backup infrastructure. Our preliminary results indicate that regional potentials for wind, solar and geothermal energy generation for electricity and heat are considerable, even when considering existing constraints, and that cross-border cooperation can contribute to meeting long-term climate goals.