This study presents an in-depth mass spectrometric investigation of dexamethasone (DEX) distribution within pharmaceutical tablets using time-of-flight secondary ion mass spectrometry (ToF-SIMS) combined with gas cluster ion beam (GCIB) sputtering. Fragmentation mechanism of DEX was identified, which enabled the determination of three-dimensional chemical imaging of the active ingredient in both surface and subsurface regions. The data reveal that a 4-mg DEX formulation exhibits a continuous and extended distribution of the drug into the tablet matrix, while a 0.5-mg formulation shows DEX localized in distinct, isolated domains. Topographical features and the overall composition of the surface were confirmed by complementary analyses employing atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS). These results demonstrate how molecule distribution patterns can be linked to formulation heterogeneity using advanced mass spectrometric techniques, opening new possibilities for pharmaceutical manufacturing quality control and optimization.