The present study concerns with an optimization method of Solid Oxide Fuel Cell (SOFC) systems for electricity generation, directly fed by CH4 (methane) or C2H5OH (ethanol). By considering a detailed thermodynamic analysis, an innovative simulation model, namely THERMAS (THERmodynamic MAthematical Simulation), was designed and implemented. A specific SOFC-based system was selected to be the reference simulation, which is assumed to be equipped with heat exchangers (preheaters), a reformer, a SOFC-stack system and an afterburner. THERMAS allows for an extended parametric analysis in terms of energy and exergy and offers the opportunity to investigate all the operational characteristics that affect system's efficiency. The optimization process relies on the difference between the energy and exergy efficiency, where an OPF (OPtimization Factor) has been introduced and particularly estimated for each simulated scenario, based on several operational parameters, such as fuel composition, extension of chemical reactions and temperatures. The introduction of this OPF is actually an innovative improvement towards an easy-to-use optimization of SOFC systems. It is found that the design of a SOFC-based power plant fueled by pure hydrocarbons, has to be carefully simulated before its, otherwise the purification of fuels sounds meaningless.