Combinatorial methods were used for studying dewetting of thin hydrophobic polystyrene (PS) and hydrophilic poly(DL-lactic acid) (PDLA) films on chemically modified gradient energy surfaces. Substrate libraries were prepared by immersing passivated Si (Si-H surface functionality) in Piranha solution (H2SO4/H2O2/H2O) at acontrolled rate, yielding a systematic variation of solvent contact angles across the surface. Additionally, chlorosilane-treated Si surfaces were exposed to UV radiation in a gradient fashion under ozone atmosphere such that a range from hydrophobic to hydrophilic conditions was obtained across the surface (≈ 3 cm). Solvent droplet contact angles of water and diiodo methane were used to quantify the spatial variation of surface energy along one axis across the surface. Libraries of thin films of PS or PDLA coatings on gradient energy surfaces orthogonal to gradients in film thickness were screened for dewetting behavior using automated optical microscopy. Contrasting trends in the wettability of PS and PDLA were visibly apparent as a function of surface energy of the substrate. The number density of polygons of the dewet PS films was found to obey a power law relationship with both film thickness and substrate surface hydrophilicity.