Described are embodiments for generating a design (e.g., a metrology mark or a device pattern to be printed on a substrate) that is optimized for aberration sensitivity related to an optical system of a lithography system. A metrology mark (e.g., a transmission image sensor (TIS) mark) is optimized for a given device pattern by matching the aberration sensitivity of the metrology mark with the aberration sensitivity of the device pattern. A cost function that comprises the aberration sensitivity differences between the metrology mark and the device pattern is evaluated based on imaging characteristic response (e.g., a critical dimension (CD) response to focus) obtained from simulation models that simulate lithography. The cost function is evaluated by modifying the metrology mark until the cost function is minimized and an optimized metrology mark is output when the cost function is minimized.