Background: Platinum-resistant ovarian cancer with peritoneal metastases remains a therapeutic frontier marked by limited systemic efficacy and a persistent unmet clinical need for effective locoregional strategies. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel minimally invasive platform designed to enhance intraperitoneal drug distribution and overcome biological barriers to chemotherapy delivery. Methods: We performed a PRISMA-compliant systematic review and meta-analysis evaluating clinical outcomes of PIPAC in platinum-resistant ovarian cancer. Primary endpoints included histologic regression (PRGS ≤ 2), severe toxicity, and 12-month overall survival, complemented by exploratory analyses of treatment feasibility, disease burden dynamics, and bidirectional therapy strategies. Results: PIPAC demonstrated a consistent signal of biologic activity, with pooled histologic response rates indicating meaningful tumor regression despite advanced disease. Severe toxicity remained low across studies, supporting the favorable tolerability of repeated intraperitoneal treatment. Survival outcomes were clinically relevant for a heavily pretreated population, while feasibility analyses suggested that PIPAC may facilitate downstream surgical opportunities in selected patients. Exploratory findings further supported the concept of intraperitoneal disease modulation, reflected by reductions in peritoneal cancer index and integration within multimodal treatment pathways. Conclusions: Beyond a purely palliative intervention, PIPAC may represent a biologically active component of personalized treatment strategies for platinum-resistant ovarian cancer. These findings redefine the therapeutic narrative from symptom control toward disease modulation and treatment escalation, underscoring the need for prospective trials to refine patient selection and optimize multimodal sequencing.