We present a fully automated quantum chemistry (QM)-based workflow that automatically identifies nucleophilic and electrophilic sites and computes methyl cation affinities (MCAs) and methyl anion affinities (MAAs) to quantify nucleophilicity and electrophilicity, respectively. The workflow shows strong correlations against experimental data from Mayr's database with R 2 coefficients of 0.84 and 0.94 for the comparison of MCAs and MAAs to experimental N • s N and E values, respectively. Furthermore, the workflow achieves similar performance as higher-level PBE0-D3(BJ)/DEF2-TZVP COSMO(∞) calculations with R 2 coefficients of 0.98 and 0.99 for MCAs and MAAs, respectively, while having a median wall time of less than two minutes per molecule.