This paper details a combination of experimental and theoretical design analyses of a cartridge-based microchannel reformer system capable of integrating two or three separate reforming processes (reactant preheating, methanol steam reforming, and methanol combustion for autothermal operation) within a single monolithic device in a two-dimensional or radially layered distribution pattern. This system employs a ceramic microchannel cartridge with catalyst configurations tailored to enable stable autothermal operation over a broad range of reforming and combustion flow rates. Operation of the 25-channel prototype system coupling methanol combustion in air (13 mol % CH3OH and 17.3 mol % O-2) with steam reforming of a dilute (2.6 mol %) methanol-water mixture at combustion and reforming overall flow rates of 300 standard cubic centimeters per minute (sccm) [gas hourly space velocity (GHSV) of 19 200 h(-1)] and 1800 sccm (GHSV of 14 400 h(-1)) achieved steam reforming hydrogen yields of similar to 85%, corresponding to an overall hydrogen yield of 53%. When the outer layer of microchannels is employed for preheating of the reforming stream, the overall hydrogen yield was improved to 57%. A three-dimensional simulation of the microchannel reformer was constructed and validated through comparison to experimental data and then employed to predict the reformer performance using a concentrated (25 mol % CH3OH and 75 mol % H2O) steam reforming feed. Design simulations predict that hydrogen yields of similar to 80% are achievable using the cartridge-based ceramic microchannel reformers.