BACKGROUND: While radiotherapy (RT) and chemotherapy (CT) significantly improve breast cancer outcomes, they may affect breast reconstruction by causing vascular damage and delayed wound healing. This retrospective study evaluates how preoperative RT, CT, or the combination of both impacts intraoperative and postoperative outcomes in immediate or delayed deep inferior epigastric perforator (DIEP) flap breast reconstructions. METHODS: We conducted a single-center review of all patients undergoing autologous DIEP flap reconstruction after mastectomy between 2018 and 2024. Patients were divided into four groups: RT only, CT only, a combination of RT and CT, and a control group with no preoperative therapies. Intraoperative and postoperative outcomes were then compared among these groups, with statistical significance defined as RESULTS: We included 114 patients representing 141 DIEP-flap breast reconstructions. Flap survival rate was 98.5%. In the univariate analysis, total microvascular recipient site complications were significantly higher in the RT + CT group (14.0%, CONCLUSIONS: Combined RT + CT significantly increased microsurgical complications. Ischemia time correlated with higher odds of total recipient site complications. Individualized patient management and diminished ischemia time are likely to improve flap survival.