The effectiveness of therapeutics is largely determined by their ability to reach the right tissues, cells, and subcellular compartments. To better understand the efficacy and potential side effects of therapeutics, it is essential to map their distribution within biological systems. In recent years, our lab, together with our collaborators, has developed and demonstrated a multimodal correlative imaging approach that combines light, electron, and NanoSIMS imaging, allowing for the visualization of a diverse range of therapeutics at subcellular resolution in cells and tissues. We have mapped various small-molecule therapeutics containing elements with a low biological background, such as iodine, bromine, and arsenic. Additionally, we have employed elemental and isotope labeling to enhance our ability to map a broader array of therapeutics in cells and tissues, including nucleic acid-based therapeutics. Our studies revealed therapeutics target distinct subcellular compartments, and subcellular drug compartmentalization affects overall drug efficacy.