The present invention relates to lithographic apparatuses and processes, and more particularly to multiple patterning lithography for printing target patterns beyond the limits of resolution of the lithographic apparatus. A method of splitting a pattern to be imaged onto a substrate via a lithographic process into a plurality of sub-patterns is disclosed, wherein the method comprises a splitting step being configured to be aware of requirements of a co-optimization between at least one of the sub-patterns and an optical setting of the lithography apparatus used for the lithographic process. Device characteristic optimization techniques, including intelligent pattern selection based on diffraction signature analysis, may be integrated into the multiple patterning process flow.