Background: To investigate the impact of residual disease after cytoreductive surgery for epithelial ovarian cancer (EOC) on survival outcomes in the era of targeted maintenance approaches, including bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitor administration. Methods: We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on PFS and OS, we constructed a linear regression model for log-transformed median progression-free survival (PFS) and overall survival (OS). Patients with and without first-line maintenance therapy were examined. The protocol was registered in the PROSPERO (CRD42021265810). Results: In total, 97 trials with 41,799 patients were included: 2476 received PARP inhibitors, and 6920 received bevacizumab. The median rate of complete cytoreduction was 36.3% (range, 0–99.4%), regardless of the timing of surgery. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independently of the use of systemic maintenance. In subgroup analysis of patients with maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increased by 19.13% for every 10% increase in complete cytoreduction rates. The previously described significant effect of total macroscopic tumor clearance of PFS could not be retained when adjusting for maintenance treatment. Conclusions: Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction in the era of novel targeted systemic agents.