The thermodynamic and kinetic behavior of water in nano-scale confinement plays an important role in biophysical phenomena such as hydrophobically-driven self-assembly. Using advanced sampling techniques, we investigate computationally the role of the substrate’s mechanical properties on the thermodynamics and kinetics of nano-scale drying transitions. We find that a single order of magnitude reduction in the material’s modulus causes the evaporation rate to increase by nine orders of magnitude. Free energy calculations show that making the confining material more flexible stabilizes the confined vapor with respect to the liquid. These findings may have implications for the function of membrane-bound protein assemblies.