Cardiotoxicity is the most dramatic complications of cancer therapies, leading to halt in potentially life-saving anti-tumor treatment regimens and a poor survival prognosis in a non-negligible percentage of patients. Angiotensin converting enzyme inhibitors (ACEIs) and β-blockers are effective in the treatment of the cancer therapy–related cardiac dysfunction (CTRCD), while their roles in the prevention of cardiotoxicity are unclear. Sacubitril/valsartan was advantageous over ACEI in heart failure patients for further reduction of cardiovascular death or heart failure re-hospitalization. However, there is short of well-established testimony of its efficacy and safety in the prevention and treatment of CTRCD in the cardio-oncology setting. Although some small observational studies found a good performance of sacubitril/valsartan in patients with CTRCD, large-scale prospective clinical studies are required to confirm its excellent results. In this paper, we review the potential benefit of sacubitril/valsartan in human subjects with CTRCD.