We report a molecular simulation investigation of the hydration thermodynamic behavior of purely siliceous, hydrophobic zeolites, in which an increasing amount of hydrophilic surface defects were introduced. An internal surface defect can either be “weak” or “strong”, depending on the balance between the defect-water and the water-water interactions. We found that the hydration behavior in presence of weak or strong defects were markedly different. The water hydration process in presence of weak surface defects is basically a homogeneous nucleation process. The effect of the weak hydrophilic defects is to make the framework overall more attractive, and this leads to the progressive shift of the condensation transition, while the framework remains overall hydrophobic. In the case of strong defects, water condensation is characterized by a combination of a strong adsorption of a limited amount of water at very low pressure, followed by a plateau in the intermediate pressure range and by a sudden filling of the nanoporous volume at higher pressure. A progressive change from hydrophobic to hydrophilic behavior is observed, as the defect content is increased. This work provides an insight from adsorption thermodynamics on the issue of hydration of geometrically and chemically heterogeneous pore surfaces. We find that a small increase in hydrophilicity of the porous framework may turn the pore from being dry to being completely filled with water at saturation conditions. We finally discuss the relevance of these results with respect to the issue of hydration of biomolecules and especially the process of high pressure protein denaturation.