In the framework of the Integrated Assessment Models (IAMs), the nexus approach is a systematic way to explore the interaction and interdependency between the climate, land, energy, and water (CLEW) systems in terms of synergies and trade-offs among themselves. The exploitation of dynamic relationships between CLEW domains should allow informed planning and policy decisions. The aim of the thesis is to perform an integrated water-energy system assessment for an isolated Mediterranean area, the Pantelleria island. A flexible, open access energy system optimization modeling framework (the Python-based TEMOA) has been selected to integrate the energy system and water system modeling. The structures of energy and water systems are first modelled considering production, distribution, and demand sectors, with a detailed sub--sectorial description.