Postoperative hospital-acquired infection in gynecologic malignancies is a severe complication, and improper treatment can affect the recovery and survival of patients. In this study, we analyzed the characteristics and distribution of pathogenic bacteria and their drug resistance in postoperative nosocomial infections in gynecologic malignancies to provide reliable guidance for clinical pharmacological monitoring. A total of 103 patients with postoperative infection following a gynecologic malignant tumor matching the inclusion criteria were selected from those who visited the gynecologic oncology department of Ganzhou Cancer Hospital/Ganzhou Cancer Center. On the day of hospital infection diagnosis, the patients’ secretions were collected and subjected to bacterial culture and drug-sensitivity tests before administering antibacterial medications. Furthermore, the distribution of pathogenic bacteria and drug-resistance characteristics of hospital infections were analyzed. A total of 127 pathogenic strains were cultured from 103 patients. The urinary tract, surgical incision site, genital tract, and pelvis were the primary infection targets, with the infection rates of 31.07%, 26.21%, 18.45%, and 11.65%, respectively. While 87.80% of Escherichia coli strains were resistant to ampicillin and methicillin/sulfamethoxazole, 100.00% and 60.00% of Klebsiella pneumoniae demonstrated resistance to ampicillin and tetracycline, respectively. All Staphylococcus epidermidis strains resisted cefotaxime, ceftriaxone, cefazolin, cefuroxime, erythromycin, benzocillin, and penicillin, while 83.34% of them showed resistance to ampicillin and methicillin/sulfamethoxazole. All Staphylococcus aureus strains were resistant to penicillin. Postoperative hospital-acquired infections following gynecologic malignancies are characterized by a diverse array of pathogenic bacteria with high drug resistance. A comprehensive assessment of the infectious condition is required with the assistance of a clinical pharmacist, accompanied by a scientific and suitable treatment plan for the patient based on the results of the drug-sensitivity test and monitoring of adverse reactions during treatment. The treatment strategy can be modified at any time during the treatment after considering pathogenic evidence and adverse drug effects to improve clinical efficacy.