Background: Advanced-stage ovarian cancer presents a significant therapeutic challenge, with primary cytoreductive surgery (PCS) followed by chemotherapy and neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS) as the two main treatment modalities. This study aims to compare the clinical outcomes, surgical complexity, and survival rates between these approaches and to assess the impact of molecular markers such as BRCA and HRD status. Methods: This retrospective, single-center observational study included 100 patients diagnosed with stage III-IV high-grade serous ovarian cancer. The patients were divided into two cohorts based on their treatment strategy: PCS followed by adjuvant chemotherapy or NACT followed by IDS. Clinical outcomes, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were analyzed, along with the impact of genetic biomarkers. Results: No statistically significant differences were observed in OS and PFS between the two treatment approaches. Patients who underwent NACT followed by IDS had lower surgical complexity scores and reduced perioperative morbidity. The HRD-positive patients exhibited improved responses to PARP inhibitors, reinforcing the significance of molecular profiling in therapeutic decision-making. The KELIM scores demonstrated prognostic relevance, particularly in the patients receiving neoadjuvant chemotherapy. Conclusion: Both PCS and NACT-IDS are viable treatment options for advanced ovarian cancer, with similar survival outcomes. The choice between strategies should be tailored based on patient-specific factors, including tumor burden, performance status, and molecular profile. The integration of biomarkers such as BRCA mutations and HRD status into clinical practice can further refine treatment selection and improve personalized management strategies.