Despite improvements in operative management and therapies, overall survival rates in advanced ovarian cancer have remained largely unchanged over the past three decades. Although it is possible to identify high-risk patients following surgery, the knowledge does not provide information about the genomic aberrations conferring risk, or the implications for treatment. To address these challenges, we developed an integrative pathway-index model and applied it to messenger RNA expression from 458 patients with serous ovarian carcinoma from the Cancer Genome Atlas project. The biomarker derived from this approach, IPI59, contains 59 genes from six pathways. As we demonstrate using independent datasets from six studies, IPI59 is strongly associated with overall and progression-free survival, and also identifies high-risk patients who may benefit from enhanced adjuvant therapy.