Halogenated derivatives of heteroaromatics and benzene derivatives are often applied as substrates in carbon-carbon and carbon-heteroatom cross-coupling reactions and are typically prepared by electrophilic aromatic substitution (EAS). However, it is often not a priori obvious at which position(s) halogenation will occur for compounds in the late stages of the synthesis that contain multiple (hetero)aromatic rings or in compounds that contain both heteroarene and benzene rings. Consequently, organic chemists tend to install the halogens early in the synthesis, thereby effectively eliminating a large number of otherwise promising synthetic routes. This is not only a problem for the synthetic chemists but also developers of software that automatically construct retrosynthetic routes. Several predictive tools have been developed to address this problem based on heuristics, 10 quantum chemical calculations (QM), machine learning (ML), or a combination of QM and ML. 14, One of these methods is the RegioSQM method developed by Kromann et al. (referred to hereafter as RegioSQM18). RegioSQM18 uses the semiempirical PM3 method and the COSMO continuum solvation model 17 implemented in the MOPAC program. MOPAC is a closed-source software package that is free to academics but not to industry, so we decided to investigate open source alternatives for further development of RegioSQM. In this paper, we show that the open source semiempirical software package xtb can be used in place of MOPAC without impacting the accuracy of the predictions. We go on to show that the accuracy can be increased by considering different tautomeric forms of the molecule and offer a qualitative prediction of the reactivity of each tautomer. Finally, we compare the accuracy of the new version (RegioSQM20) to two ML-based models for regioselectivity predictions.