A central challenge in drug development is determining whether a therapeutic achieves appropriate tissue distribution and produces biologically meaningful effects. We present a drug-inclusive spatial analysis approach capable of spatially imaging small molecules, antibody-based therapeutics, or oligonucleotide drugs within intact tissue while simultaneously mapping proteins, RNA, lipids, metabolites, and glycans from the same section. Using an Alzheimer’s disease mouse model, we illustrate the approach with a model compound, visualizing regional drug distribution alongside molecular signatures of pathology and neuroinflammation. An AI-powered correlative spatial analytics pipeline integrates these layers to align drug distribution with biological effect in situ, accelerating mechanism confirmation and de-risking critical development decisions.