Optimizing the buffer layer in manufactured thin-film PV is essential to maximize device efficiency. Here, we describe a combined synthesis, characterization, and theory effort to design optimal buffers based on the (Cd,Zn)(O,S) alloy system for CIGS devices. Optimization of buffer composition and absorber/buffer interface properties in light of several competing requirements for maximum device efficiency were performed, along with process variations to control the film and interface quality. The most relevant buffer properties controlling performance include band gap, conduction band offset with absorber, dopability, interface quality, and film crystallinity. Control of an all-PVD deposition process enabled variation of buffer composition, crystallinity, doping, and quality of the absorber/buffer interface. Analytical electron microscopy was used to characterize the film composition and morphology, while hybrid density functional theory was used to predict optimal compositions and growth parameters based on computed material properties. Process variations were developed to produce layers with controlled crystallinity, varying from amorphous to fully epitaxial, depending primarily on oxygen content. Elemental intermixing between buffer and absorber, particularly involving Cd and Cu, also is controlled and significantly affects device performance. Secondary phase formation at the interface is observed for some conditions and may be detrimental depending on the morphology. Theoretical calculations suggest optimal composition ranges for the buffer based on a suite of computed properties and drive process optimizations connected with observed film properties. Prepared by LLNL under Contract DE-AC52-07NA27344.