Methods and systems for diagnosing a semiconductor wafer are provided. A first raw image, a second raw image, and a third raw image of the semiconductor wafer are obtained by an inspection apparatus according to graphic data system (GDS) information regarding layout of a target die. A first image-based comparison is performed by a determining circuitry on the first, second, and third raw images, so as to provide a comparison result. The comparison result indicates whether an image difference is present between the first, second, and third raw images.