The application of high-temperature fuel cells in Waste Water Treatment Plants (WWTPs) combines a high-efficiency electricity generation technology and a renewable fuel, thus simultaneously mitigating greenhouse gas emissions and resource depletion. This study investigates the current applicability and limitations of biogas-powered Molten Carbonate Fuel Cells (MCFCs) Solid Oxide Fuel Cells (SOFCs) and compares them with Internal Combustion Engines (ICEs) and micro-turbines (MTs). Operational data from six industrial-scale plants and from a pilot plant was collected to simulate the performance of these Energy Conversion Systems in twelve scenarios, built based on two WWTP sizes (100,000 and 500,000 PE) and two biogas qualities (H2S 2500 and 250 ppmv). Comparisons were focused on technical (Normalized Saved Fossil Energy and percentage of energy self-sufficiency) and economic (Levelized Cost of Energy and Payback Period/Internal Rate of Return) indicators. MCFCs showed the highest technical performance, improving the electrical self-sufficiency of the WWTP around 60% compared to conventional cogeneration. However, to date, ICEs are still the most economically profitable alternative, as payback periods of fuel cell projects are 4 times larger. The high investment cost and the low stack durability are the key parameters to be improved for industrial deployment of fuel cell systems in WWTPs