Practical case studies showed that our methods could reliably distinguish unreactive molecules from reactive ones. For the copper-free click reactions, the ring strain release gap is around 7 kcal/mol between the reactive cyclooctynes and the nonreactive molecules. For the ROMP reactions, norbornene derivatives need around 15 kcal/mol ring strain energy to be thermodynamically favored. These applications demonstrated the transferability and practical value of the AIMNet2 RSE workflow.