A number of wafers of a semiconductor device are inspected to generate a plurality of wafer inspection data. A method for identifying critical hot spots to improve lithographic process of manufacturing the semiconductor device uses design signature analytics according to the plurality of wafer inspection data with reference to the design data of the semiconductor device. Design signature analytics includes global alignment, full chip pattern correlation, pattern characterization and design signature inference. The global alignment compensates for the physical coordinate offsets between the chip design data and the wafer inspection data. The full chip pattern correlation uses multi-stage pattern matching and grouping to identify highly repeating defects as hot spots. Pattern characterization extracts the design patterns and design signatures of the highly repeating defects. Design signature inference analyses the design signatures, identifies critical design signatures and determines the criticality of the critical design signatures.