A system and method for deriving semiconductor manufacturing process corners using surrogate simulations is disclosed. The method may be used to determine individual performance metric yields, the number of out-of-specification conditions for a given number of simulation samples, and a total yield prediction for simultaneous multi-variable conditions. A surrogate simulation model, such as a Response Surface Model, may be generated from circuit simulation data or parametric data measurements and may be executed using a large number of multi-variable sample points to determine process corners defining yield limits for a device. The model may also be used to simulate process shifts and exaggerated input ranges for critical device parameters. In some embodiments, the derived process corners may better represent physically possible worst-case process corners than traditional general-purpose process corners, and may address differences in process sensitivities for individual circuits of the device.