Protein interaction networks are fundamental to understanding cellular biology, disease mechanisms, and therapeutic strategies. By studying these networks, researchers can identify new drug targets and develop more effective therapies, ultimately improving health outcomes for patients. In this presentation, we will explore how interactomic technologies, particularly proximity labeling mass spectrometry, are being leveraged to accelerate various stages of drug discovery. Beginning with the initial phases of target assessment and validation, we will demonstrate how interactomic technologies can be leveraged to elucidate novel biological mechanisms and map cell type-specific interactomes at discrete subcellular localizations. Understanding the spatiotemporal behavior of these networks can help guide target selection, therapeutic approaches, and development of target engagement pharmacodynamic assays. We will next discuss how interactomic technologies can be applied in chemical matter screens aimed at identifying promising lead compounds for induced proximity strategies like targeted protein degradation, where the therapeutic approach hinges upon creating or strengthening protein-protein interactions. Finally, we will discuss how interactomic technologies can be used to elucidate unknown drug mechanisms, such as target deconvolution for drugs found in phenotypic screens or identification of off-targets to design more effective and safer therapeutics.