Liquefied natural gas (LNG) is regarded as the cleanest among fossil fuels due to its lower environmental impact. In power plants, it emits 50−60% less carbon dioxide into the atmosphere compared to regular oil or coal-fired plants. As the demand for a lower environmental footprint is increasing, fuel cells powered by LNG are starting to appear as a promising technology, especially suitable for off-grid applications, since they can supply both electricity and heating. This article presents a techno-economic assessment for an integrated system consisting of a solid oxide fuel cell (SOFC) stack and a micro gas turbine (MGT) fueled by LNG, that feeds the waste heat to a multi-effect desalination system (MED) on the Greek island of Patmos. The partial or total replacement of the diesel engines on the non-interconnected island of Patmos with SOFC systems is investigated. The optimal system implementation is analyzed through a multi-stage approach that includes dynamic computational analysis, techno-economic evaluation of different scenarios using financial analysis and literature data, and analysis of the environmental and social impact on the island. Specific economic indicators such as payback, net present value, and internal rate of return were used to verify the economic feasibility of this system. Early results indicate that the most sensitive and important design parameter in the system is fuel cell capital cost, which has a significant effect on the balance between investment cost and repayment years. The results of this study also indicate that energy production with an LNG-fueled SOFC system is a promising solution for non-interconnected Greek islands, as an intermediate carrier prior to the long-term target of a CO₂-free economy.