Deruxtecan is primarily used as a cytotoxic payload in antibody-drug conjugates (ADCs) for targeted cancer therapy. It functions by inhibiting topoisomerase I, leading to DNA damage and ultimately inducing apoptosis in cancer cells. Due to its high potency and bystander killing effect, it is effective even against tumor cells with heterogeneous antigen expression. Deruxtecan-based ADCs have shown significant clinical activity in treating various solid tumors, including breast, gastric, and non-small cell lung cancers. Its ability to remain active in low-oxygen tumor environments and its membrane permeability enhance its therapeutic efficacy. Ongoing research continues to explore its potential in new ADC platforms and combination therapies.