Methods and systems for detecting defects on a wafer are provided. One method includes determining characteristics of care areas for a wafer based on wafer patterns. Determining the characteristics includes determining locations of care areas, identifying at least one pattern of interest (POI) in the wafer patterns for each of the care areas, allowing any of the care areas to have a free-form shape, allowing the care areas to be larger than frame images and selecting two or more POIs for at least one of the care areas. The method also includes searching for POIs in images generated for the wafer using an inspection system. In addition, the method includes detecting defects on the wafer by determining positions of the care areas in the images and applying one or more defect detection methods to the images based on the positions of the care areas in the images.