Today, in the era of precision medicine, the determination of genomic instability or other potentially targetable mutations, along with BRCA 1 and BRCA 2, is a crucial component of the diagnosis and treatment management of advanced ovarian cancer. Advanced technologies such as next-generation sequencing (NGS) have enabled comprehensive genomic profiling (CGP) analysis to become more feasible for routine use in daily clinical work. Here, we present the results for the first two years of an analysis of patients with advanced ovarian cancer on a national level. The aim was to establish the position of CGP in the daily clinical practice of treating ovarian cancer. We performed a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients who were newly diagnosed with locally advanced or metastatic ovarian cancer or whose initial disease had progressed from 1 January 2020 to 1 December 2021, and whose tumors underwent CGP analysis. All 86 patients (100%) analyzed with CGP had at least one genomic alteration (GA). The median LOH was 14.6 (IQR 6.8–21.7), with 35 patients (41%) having an LOH ≥ 16. We found BRCA-positive status in 22 patients (26%). Conventional testing, which detects only BRCA mutations, would have opted for therapy with PARP inhibitors in 22 (26%) of our patients. However, CGP revealed the need for PARP inhibitors in 35 patients (41%). The results identified a significantly higher number of women who would achieve a possible benefit from targeted therapy. Hence, we believe that CGP should be a backbone diagnostic tool in the management of ovarian cancer.