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Simple Summary: Ovarian cancer is the third most common gynecologic cancer and the eighth most common cause of death from cancer in women. Comprehensive genomic profiling (CGP) is a test that checks hundreds of genes. Changes in these genes and may help to suggest which anti-cancer treatment may be the most effective for the tested individual. As the test is expensive, and the treatments aimed at treating specific genes related to cancer are both limited and expensive, CGP is not often used. In this study, we investigated whether women with ovarian cancer who had the CGP test had better outcomes (i.e., had longer times with no advancing of disease or lived longer) than women who did not have this test. Our results suggest that women who had the CGP test lived longer than those who did not, but more studies are needed to confirm this. Comprehensive genomic profiling (CGP) allows for the detection of driver alterations at high resolution, but the limited number of approved targeted therapies and their high costs have contributed to its limited clinical utilization. We retrospectively compared data of 946 women with ovarian cancer (11.4% were referred to CGP, and 88.6% served as control) to examine whether CGP provides a prognosis benefit. Patient baseline parameters were similar between the groups. Cox regression analysis adjusted for age, disease stage at diagnosis, and recurrence status showed statistically significantly longer median overall survival (mOS) in the CGP group versus the control (73.4 versus 54.5 months, p < 0.001). Fifty-four patients (52.9%) had actionable mutations with potential treatments; twenty-six (48.2%) were treated with matched targeted therapy, showing a trend for longer mOS than the eighty-six women in the CGP group who were not given a suggested treatment (105.5 versus 63.6 months, p = 0.066). None of the genomic alterations predicted metastasis location. CCNE1 amplification and KRAS mutations were associated with shorter mOS. Patients with tumor mutation burden ≥4 mutations/megabase had longer mOS. High loss of heterozygosity was associated with longer mOS (99.0 versus 48.2 months, p = 0.004). CGP testing may provide both prognostic and predictive insights for treatment of patients with ovarian cancer. Prospective studies of larger cohorts are warranted. [ABSTRACT FROM AUTHOR]