Silica-based materials find applications as excipients and, particularly for those of mesoporous nature, as drug delivery agents for pharmaceutical formulations. Their performance can be crucially affected by water moisture, as it can modify the behavior of these formulations, by limiting their shelf life. Here we describe the role of water microsolvation on the features of ibuprofen adsorbed on a model of amorphous silica surface by means of density functional theory (DFT) simulations. Starting from the results of the simulation of ibuprofen in interaction with a dry hydrophobic amorphous silica surface, a limited number of water molecules has been added to study the configurational landscape of the microsolvated system. Structural and energetics properties, as well as the role of dispersive forces, have been investigated. Our simulations have revealed that the silica surface exhibits a higher affinity for water than for ibuprofen, even if several structures coexist at room temperature, with an active competition of ibuprofen and water for the exposed surface silanols. Dispersive interactions play a key role in this system, as pure DFT fails to correctly describe its potential energy surface. Indeed, van der Waals forces are the leading contribution to adsorption, independently of whether the drug is hydrogen-bonded directly to the surface or via water molecules.