The mean and variance of the colloid interaction energy (Phi*) as a function of separation distance (h) were calculated on physically and/or chemically heterogeneous solid surfaces at the representative elementary area (REA) scale. Nanoscale roughness was demonstrated to have a significant influence on the colloid interaction energy for different ionic strengths. Increasing the roughness height reduced the magnitude of the energy barrier (Phi(max)*) and the secondary minimum (Phi(2min)*). Conversely, increasing the fraction of the solid surface with roughness increased the magnitude of Phi(max)* and Phi(2min)*. Our results suggest that primary minimum interactions tend to occur in cases where only a portion of the solid surface was covered with roughness (i.e., isolated roughness pillars), but their depths were shallow as a result of Born repulsion. The secondary minimum was strongest on smooth surfaces. The variance in the interaction energy was also a strong function of roughness parameters and h. In particular, the variance tended to increase with the colloid size, the magnitude of Phi*, the height of the roughness, and especially the size (cross-sectional area) of the heterogeneity. Nonzero values of the variance for Phi(2min)* implied the presence of a tangential component of the adhesive force and a resisting torque that controls immobilization and release for colloids at this location. Heterogeneity reduced the magnitude of Phi* in comparison to the corresponding homogeneous situation. Physical heterogeneity had a greater influence on mean properties of Phi* than similar amounts of chemical heterogeneity, but the largest reduction occurred on surfaces with both physical and chemical heterogeneity. The variance in Phi* tended to be higher for a chemically heterogeneous solid.