Methods for determining customized defect detection inspection plans are provided. One method includes fabricating a test chip and generating test chip data from the fabricated test chip. Then, defining systematic signatures from the generated test chip data and identifying a yield relevant systematic signature from the defined systematic signatures. The method includes identifying a layout pattern associated with the yield relevant systematic signature and locating the identified layout pattern on a process module layer of a product chip. Further, the method includes defining a customized defect detection inspection or metrology methodology for detecting systematic defects on the process module layer based on the identified layout pattern associated with the yield relevant systematic signature.