In this study, the dominant intermolecular interactions at powder surfaces were investigated using inverse gas chromatography. Silica beads coated with molasses, corn starch, butter, or wheat gluten were used as model powders to emulate the interactions of surface components present in common food powders. The flow properties of the powders were analyzed using a rotational shear cell device at ambient conditions (25 °C and 40% relative humidity). A positive correlation (r = 0.72, p < 0.05) between the acid-base ratio (accounting for the ratio between the number of electron acceptor to electron donor surface sites) and the flow factor (flowability indicator, ffc at 1 kPa pre-shear stress) was observed for all the size ranges of surface-modified silica beads and industry-grade powders (modified corn starch and palm oil powders). The results depict the importance of acid-base surface components in understanding the mechanistic influence of pre-load molecular dynamics on the bulk flowability.