Recent experiments revealed that roughness decreases the gap in colloid attachment between favorable (repulsion absent) and unfavorable (repulsion present) conditions through a combination of hydrodynamic slip and surface interactions with asperities. Hydrodynamic slip was calibrated to experimentally observed tangential colloid velocities, demonstrating that slip length was equal to maximum asperity relief, thereby providing a functional relationship between slip and roughness metrics. Incorporation of the slip length in mechanistic particle trajectory simulations yielded the observed modest decrease in attachment over rough surfaces under favorable conditions, with the observed decreased attachment being due to reduced colloid delivery rather than decreased attraction. Cumulative interactions with multiple asperities acting within the zone of colloid-surface interaction were unable to produce the observed dramatic increased attachment and decreased reversibility with increased roughness under unfavorable conditions, necessitating inclusion of nanoscale attractive heterogeneity that was inferred to have codeveloped with roughness. Simulated attachment matched experimental observations when the spatial frequency of larger heterodomains (nanoscale zones of attraction) increased disproportionately relative to smaller heterodomains as roughness increased, whereas attachment was insensitive to asperity properties, including the number of interactions per asperity and asperity height; colloid detachment simulations were highly sensitive to these parameters. These cumulative findings reveal that hydrodynamic slip moderately decreases colloid bulk delivery, nanoscale heterogeneity dramatically enhances colloid attachment, and multiple interactions among asperities decrease detachment from rough surfaces.