Main‐group chalcogenides show outstanding performance for phase‐change data storage and thermoelectric energy conversion applications. A common denominator for these different property requirements has been ascribed to the metavalent bonding (MVB) mechanism. Atom probe tomography (APT) provides a unique way to distinguish MVB from other bonding mechanisms by determining the bond‐breaking behavior. Specifically, an unusually high probability to dislodge several fragments upon one successful laser pulse (‘probability of multiple events’–PME) is found in metavalently bonded crystalline phase‐change and thermoelectric materials. In contrast, amorphous phase‐change materials and poor thermoelectrics usually show lower PME values. This indicates that the large optical and electrical contrast between the crystalline and amorphous chalcogenides is attributed to a transition of chemical bonding. A strong correlation between high thermoelectric performance and large PME has also been established. Besides, APT can investigate structural defects on the sub‐nanometer scale. These characteristics reveal the inter‐diffusion of elements in interfacial phase‐change materials and revisit its switching mechanism. The complex role of structural defects such as grain boundaries in tuning the thermoelectric properties can also be unraveled by investigating the local composition and bonding mechanism at defects. This review demonstrates that APT is a powerful technique for designing phase‐change and thermoelectric materials.This article is protected by copyright. All rights reserved.