In summary, we have described a rational substituent strategy that can induce and enhance inverted singlet-triplet gaps in a range of non-alternant polycyclic hydrocarbon cores, as well as in well-known azaphenalenes. This is achieved by functionalizing with electron donors in positions with large LUMO coefficients, or with electron acceptors in positions with large HOMO coefficients. We have also found that using the reverse strategy can effectively remove the singlet-triplet gap inversion. This result underlines the importance of rational design rules. We project that this knowledge of substituent effects will enable improved screening efficiency in the hunt for novel inverted gap systems. We have provided a systematic approach for the a priori elimination of undesired core-substituent combinations from the search pool, thus reducing computational cost and reserving highly accurate methods for the most likely candidates. This strategy will also facilitate the optimization of other properties, such as oscillator strengths, while retaining an inverted singlet-triplet gap.