Heterogeneity in chemotherapeutic response is directly associated with prognosis and disease recurrence in patients with ovarian cancer (OvCa). Despite the significant clinical need, a credible gene signature for predicting response to platinum-based chemotherapy and for guiding the selection of personalized chemotherapy regimens has not yet been identified. The present study used an integrated approach involving both OvCa tumors and cell lines to identify an individualized gene expression signature, denoted as IndividCRS, consisting of 16 robust chemotherapy-responsive genes for predicting intrinsic or acquired chemotherapy response in the meta-discovery dataset. The robust performance of this signature was subsequently validated in 25 independent tumor datasets comprising 2215 patients and one independent cell line dataset, across different technical platforms. The IndividCRS was significantly correlated with the response to platinum therapy and predicted the improved outcome. Moreover, the IndividCRS correlated with homologous recombination deficiency (HRD) and was also capable of discriminating HR-deficient tumors with or without platinum-sensitivity for guiding HRD-targeted clinical trials. Our results reveal the universality and simplicity of the IndividCRS as a promising individualized genomic tool to rapidly monitor response to chemotherapy and predict the outcome of patients with OvCa.