Monolithic adsorbent systems offer the potential to achieve high throughput in fast-cycle adsorption processes. Modeling these systems is typically based on the “ideal monolith” assumption, neglecting channel nonuniformities. A new model that accounts for both structural nonuniformity and inlet flow maldistributions is presented and validated using literature data of breakthrough experiments and full-cycle process performance for carbon capture separation. A detailed comparison between predictions using an apparent mass transfer coefficient (MTC) obtained by fitting the breakthrough curve and the intrinsic MTC is presented. The process calculations based on the apparent MTC grossly underpredict the carbon dioxide recovery. A procedure is established to obtain the structural nonuniformity parameters and flow maldistribution effects from the breakthrough curve. With this model, the full-cycle predictions are within 1.20 and 1.25% of the experimental observations in terms of heavy product purity and recovery, respectively. The evidence reported in this article makes a strong case for independent measurement of the intrinsic MTCs in monolithic systems.