A method and system for performing model-based registration and critical dimension measurement is disclosed. The method includes: utilizing an imaging device to obtain at least one optical image of a measurement site specified for a photomask; retrieving a design of photomask and utilizing a computer model of the imaging device to generate at least one simulated image of the measurement site; adjusting at least one parameter of the computer model to minimize dissimilarities between the simulated images and the optical images, wherein the parameters includes at least a pattern registration parameter or a critical dimension parameter; and reporting the pattern registration parameter or the critical dimension parameter of the computer model when dissimilarities between the simulated images and the optical images are minimized.