Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) targeting TROP-2, showing promising results in the treatment of triple-negative breast cancer (TNBC). ADCs are designed to deliver cytotoxic agents selectively to cancer cells, minimizing systemic toxicity. Dato-DXd consists of a humanized anti-TROP-2 monoclonal antibody linked to a topoisomerase I inhibitor payload via a cleavable linker. TROP-2 is overexpressed in many cancers, including TNBC, making it an attractive therapeutic target. Dato-DXd has demonstrated high efficacy and manageable safety in clinical trials, with encouraging results in TNBC patients. In the TROPION-PanTumor01 trial, Dato-DXd showed an overall response rate (ORR) of 32% and a disease control rate (DCR) of 80%. In the BEGONIA trial, when combined with durvalumab, Dato-DXd achieved an ORR of 79% with a manageable safety profile. Several phase III trials are ongoing to evaluate Dato-DXd in metastatic TNBC, comparing it with standard chemotherapy. These trials aim to assess progression-free survival (PFS), overall survival (OS), and other endpoints. Dato-DXd has a long half-life, allowing for a 3-week dosing schedule, and is primarily eliminated via bile/faeces. Despite its potential, access to Dato-DXd is limited in some countries, and further real-world data are needed to fully understand its role. The combination of Dato-DXd with immune checkpoint inhibitors (ICIs) is also being explored, as ADCs may enhance immunotherapy efficacy. Overall, Dato-DXd represents a significant advancement in the treatment of TNBC, offering a new therapeutic option with a favorable safety profile.Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) targeting TROP-2, showing promising results in the treatment of triple-negative breast cancer (TNBC). ADCs are designed to deliver cytotoxic agents selectively to cancer cells, minimizing systemic toxicity. Dato-DXd consists of a humanized anti-TROP-2 monoclonal antibody linked to a topoisomerase I inhibitor payload via a cleavable linker. TROP-2 is overexpressed in many cancers, including TNBC, making it an attractive therapeutic target. Dato-DXd has demonstrated high efficacy and manageable safety in clinical trials, with encouraging results in TNBC patients. In the TROPION-PanTumor01 trial, Dato-DXd showed an overall response rate (ORR) of 32% and a disease control rate (DCR) of 80%. In the BEGONIA trial, when combined with durvalumab, Dato-DXd achieved an ORR of 79% with a manageable safety profile. Several phase III trials are ongoing to evaluate Dato-DXd in metastatic TNBC, comparing it with standard chemotherapy. These trials aim to assess progression-free survival (PFS), overall survival (OS), and other endpoints. Dato-DXd has a long half-life, allowing for a 3-week dosing schedule, and is primarily eliminated via bile/faeces. Despite its potential, access to Dato-DXd is limited in some countries, and further real-world data are needed to fully understand its role. The combination of Dato-DXd with immune checkpoint inhibitors (ICIs) is also being explored, as ADCs may enhance immunotherapy efficacy. Overall, Dato-DXd represents a significant advancement in the treatment of TNBC, offering a new therapeutic option with a favorable safety profile.