Sorption-Enhanced Steam Methane Reforming (SE-SMR) is a promising technology for effective production of hydrogen with simultaneous CO2 capture from conventional fuels (e.g. methane, coal) and alternative fuels (e.g. biomass). SE-SMR combines steam methane reforming reaction and water-gas shift conversion reaction with a high temperature CO2 sorption system using a mixture of solid catalyst and sorbent. In this work, a methodology that combines Taguchi robust Design of Experiments (DoE) with previously validated CFD simulations [19] is presented. The main objective is to carry on a multi-criteria analysis of the effect of different sorbents and pretreatments and operation parameters in the response of the 500 kW(th) bubbling fluidized bed (BFB) reactor installed in the ZECOMIX (Zero Emissions of CarbOn with MIXed technologies) research infrastructure of ENEA. The effect of different sorbents (i.e. naturally occurring dolomite and synthetic CaO-Ca12Al14O33) and pretreatment seems to be negligible at high scales compared with heat and mass transfer mechanisms. Other parameters (i.e. temperature, pressure, particle diameter, gas velocity, bed height, presence of catalyst and sorbent, treatment of sorbent, syngas composition) have been also evaluated. The present methodology can be a useful approach for a preliminary design and optimization of a full-scale SE-SMR reactors.