A method of efficient optical and resist parameters calibration based on simulating imaging performance of a lithographic process utilized to image a target design having a plurality of features. The method includes the steps of determining a function for generating a simulated image, where the function accounts for process variations associated with the lithographic process; and generating the simulated image utilizing the function, where the simulated image represents the imaging result of the target design for the lithographic process. Systems and methods for calibration of lithographic processes whereby a polynomial fit is calculated for a nominal configuration of the optical system and which can be used to estimate critical dimensions for other configurations.