This invention discloses diagnosis of risk of chemotherapy-induced cardiotoxicity by measurement of increased expression of soluble epoxide hydrolase in vitro and in vivo in cells, tissues or animals including measurement of increased levels of soluble epoxide hydrolase metabolites, e.g., 14,15-DHET and 11,12-DHET, in biological fluids. This invention also includes diagnosis of risk of chemotherapy-induced cardiotoxicity by measuring increased levels of oxidative stress in cells, tissues or animals including measurement of increased levels of oxidative stress biomarkers, e.g., 8-isoprostane, in biological fluids. Fatty acid and protein biomarkers to diagnose the risk of chemotherapy-induced cardiotoxicity are detected using various detection methods including mass spectrometry and immunoassay such as ELISA, Western blot analysis or label-free microwell and nanowell technologies. This invention discloses targeted medical intervention for a subject who is at risk or with chemotherapy-induced cardiotoxicity by treating with soluble epoxide hydrolase inhibitor(s) with or without antioxidants to prevent or ameliorate the chemotherapy-induced cardiotoxicity.