In order to elucidate these QSPRs, we employed an explosophore-based approach to describe and classify HEMs based on the presence of energetic functional groups known as explosophores (Figure ), typical examples of which include nitro groups, nitramines, azides, and nitrogen-containing heterocycles. Explosophores are widely acknowledged to be responsible for the initial mechanistic steps leading to the deflagration or detonation of an HEM. As such, detailed molecular description of explosophores is paramount in the development of chemically interpretable predictive models that can guide the design of next-generation HEMs. To enable this study, we compiled a highly diverse sensitivity property database containing over 400 HEMs reflecting prevailing trends in energetics research (Figure ). To capture the mechanistic importance of explosophores, we designed a general set of structural and quantum mechanical descriptors that can be applied to any type of explosophore, yielding a rich description of the chemical structures responsible for decomposition events. This descriptor ensemble includes natural bond orbital (NBO) analysis, Hirshfeld surface analysis, vibrational frequencies, charges, and the molecular geometry of explosophores. With this descriptor set in hand, we employed MLR modeling to develop chemically interpretable predictive models for the decomposition temperature and impact sensitivity of tetrazole and azide HEMs (Figure ). Through several case studies, we demonstrate the versatility of our explosophore-based approach for accurate prediction of HEM sensitivity properties and identification of structure-property correlations useful in rational design, as well as for corroboration of proposed decomposition mechanisms.