Introduction <p>Hernia repair following cancer surgery is often challenging due to prior radiation therapy, malnutrition, and immunosuppression. Poly-4-hydroxybutyrate (P4HB) is a biosynthetic mesh that balances strength and biocompatibility, potentially optimizing outcomes in this high-risk population. This study aimed to evaluate recurrence and surgical site complications associated with P4HB mesh in oncologic patients undergoing incisional hernia repair and to identify surgical techniques related to improved outcomes.</p> Methods <p>Patients with previous oncologic abdominal or pelvic surgery who developed an incisional hernia and underwent surgical repair using P4HB from January 2018 to December 2023 were identified. Patients were analyzed according to wound classification. Primary outcomes included hernia recurrence and surgical site complications (hematoma, infection/cellulitis, superficial wound dehiscence, and abscess formation).</p> Results <p>102 patients [median (IQR) age 63 (55–69) years; median BMI 26 (23–30) kg/m²] were included, with a median follow-up of 26.1 (15.1–40.1) months. The overall recurrence rate was 8.8%, significantly differing between clean (Class I) and contaminated (Class II-IV) cases (0% vs. 17%, <i>p</i> = 0.003). Surgical complications occurred in 24% of patients, with seroma (8.8%) and superficial wound dehiscence (7.8%) being the most common, and complication rates comparable between wound classifications. Bilateral external oblique release (HR, 0.16; 95% CI, 0.04–0.65; <i>p</i> = 0.01) and retrorectus mesh placement (HR, 0.05; 95% CI, 0.01–0.36; <i>p</i> = 0.004) were independently associated with reduced recurrence.</p> Conclusion <p> P4HB mesh in incisional hernia repair for oncologic patients yields low recurrence rates and acceptable complication rates. Bilateral external oblique release and retrorectus mesh placement are surgical techniques significantly associated with improved outcomes.</p>