Currently the production of methanol from Refuse Derived Fuel, a derived product of Municipal Solid Waste, can be deemed as an excellent example of circular economy, by representing a promising alternative both to conventional methods of waste disposal and methanol production from fossil resources. High-temperature conversion of waste in syngas is the main step of the Waste-to-Methanol process. Unfortunately, produced syngas does not directly comply with the requirements for methanol synthesis, in that syngas purification and conditioning steps are required. Moreover, waste, due to its heterogeneous nature, presents a variable composition, leading to the production of variable syngas flowrate and composition. A thermodynamic equilibrium model of gasification unit has been developed in Aspen Plus environment and applied to analyse the effects of feedstock variability; RDF composition has been characterized considering as main parameters: ash, moisture and combustible fractions, carbon to hydrogen and carbon to oxygen ratios, and Lower Heating Value. Then, a simplified simulation of downstream process has been introduced to evaluate the influence of waste composition on overall methanol production. The present study allows the identification of the main parameters affecting the syngas and, accordingly, overall process yield, consumptions and emissions.