XRD-DSC is a simultaneous measurement technique that integrates X-ray diffraction (XRD) with differential scanning calorimetry (DSC), allowing real-time observation of both thermal and structural changes under controlled temperature and humidity. This dual approach enables comprehensive analysis of material behavior, serving as a complementary method to the individual techniques. XRD-DSC has been widely used in pharmaceuticals, food engineering, and polymers, offering significant benefits in product development and quality control. This report outlines the principles of XRD-DSC, how to interpret profiles, and recent application examples. In acetaminophen, XRD-DSC captured transitions between metastable polymorphs during heating. For nedocromil sodium, humidity-controlled measurements revealed the transformation from monohydrate to trihydrate at 20 %RH, while TG-DTA confirmed dehydration from trihydrate upon heating. In food applications, butter's structural changes—particularly in lamellar and subcell structures of triacylglycerols—were tracked through thermal cycling, linking thermal history to textural quality. These results highlight XRD-DSC as a powerful and precise tool for evaluating structural and thermal properties simultaneously. Its versatility makes it valuable for optimizing formulation, processing, and storage across diverse industries.