Positive Energy Districts (PEDs) enable to address the challenge of the urban energy transition from a bottom-up perspective. However, their effective implementation is currently restrained by several barriers mainly issued from their novelty. In that context, there is a need for moving from theory to practice through the development of instruments that support practitioners in the planning and application of PEDs. The present paper introduces a novel methodology for Mediterranean cities, an area facing several multidisciplinary challenges in its energy transition pathway. Concretely, the methodology has the ambition to support the execution of a four-step process to generate a transition scenario to convert existing districts into PEDs. In the first step, a multi-criteria decision analysis is conducted to identify and select the most suitable areas for PEDs implementation. Then, the second step is dedicated to the iterative technical design of the PED consisting of the selection of solutions and their integration within the district. After that, the third step focuses on incorporating the district’s social and economic ecosystem into the design. Finally, the last step leads to the generation of the transition scenario. Through this methodology, the paper aims to support the inclusion of PEDs in the planning strategies of Mediterranean cities.