The continuous increase in the energy demand and the reduction on fossil fuels reservoirs has shifted interest towards more "green" alternatives for decentralized power production. This study focuses on the design optimization and performance assessment of a small-scale, low-temperature solar driven ORC for application in South-East Mediterranean region under multiple scenarios including different working fluids, installation sites and solar collector types. For each scenario, a multi-objective genetic optimization algorithm is implemented to minimize the payback period and maximize the mean exergy efficiency considering annual operation. The optimization concluded that the correlation between the solar field area and the optimization parameters is more complicated and directly connected to the climatic conditions of each considered location. The maximum achieved exergy efficiency is about 6.2% for an ORC running with R245fa coupled with evacuated tube collectors in Istanbul. The minimum payback period was reported for the case of Larnaca, Cyprus, considering an ORC coupled with parabolic trough collectors and operating with R152. Finally, the annual net electricity production of the ORC was translated in primary energy savings. It was calculated that in all locations R152a achieved the highest savings for the maximum area of the solar field. (C) 2020 Elsevier Ltd. All rights reserved.