Simple SummaryCancer therapy-related cardiac dysfunction (CTRCD) has been an urgent medical issue in patients that receive breast cancer therapies including anthracycline-based chemotherapies and/or targeted anti-HER2 therapies such as trastuzumab. Traditional biomarkers used as standard of care may be useful indicators of cardiac damage but their use to predict the onset of CTRCD lacks reliability. Ongoing clinical studies aim to explore new insights into the use of traditional biomarkers and investigate the promising role of novel biomarkers as reliable indicators and/or predictors of CTRCD. Patients with breast cancer could benefit from an alternative cardiac risk stratification plan that has the potential to predict the onset of CTRCD and/or detect CTRCD at early stages. The aim of this systematic review is to provide an overview of the human studies, which explore novel insights into traditional biomarkers and/or novel biomarkers that can be used for the early detection and/or prediction of CTRCD in breast cancer patients undergoing cardiotoxic-cancer therapies.AbstractCardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD.