Unlike our previous NMR-based method, RegioSQM considers all aromatic CH positions. The software correctly predicts the low reactivity of fluorinated arenes and generally accounts for the high reactivity of 1,2,4-triazoles, both of which represent improvements over the original method. RegioSQM is fully automated and straightforward to use requiring only the SMILES string of the molecules of interest as input. Importantly, this means that neither computationally demanding density functional theory calculations, that are difficult to perform by non-expert users, nor visual inspection of the HOMO orbitals are required to obtain solid predictions regardless of the nature of the substrates. Finally, RegioSQM predicts the specific reactive sites correctly in 81% of the cases as compared to approximately 60% when basing predictions on the chemical shifts calculated using ChemDraw. RegioSQM is thus a much improved method compared to our NMR-based original approach.