Background <p>Tubo-ovarian abscess (TOA) is a severe complication of pelvic inflammatory disease (PID). Conservative antibiotic therapy is the preferred first-line treatment; however, treatment failure necessitates surgical intervention in a subset of patients. This study aimed to identify risk factors associated with antibiotic treatment failure in TOA through a systematic review and meta-analysis, thereby providing evidence for clinical decision-making.</p> Methods <p>A systematic search was conducted in PubMed, Embase, the Cochrane Library and Web of Science to identify controlled studies on risk factors for antibiotic treatment failure in TOA published between database inception and December 2025. The Newcastle–Ottawa Scale was used to assess the quality of the literature. Mean differences (MDs) or odds ratios with 95% confidence intervals were calculated. Heterogeneity was assessed using the <i>I</i>^<i>2</i> statistic and the Q test.</p> Results <p>Thirteen studies involving 1,759 patients were included. The meta-analysis revealed that patients in the antibiotic treatment failure group were significantly older (MD = 3.61 years, <i>P</i> &lt; 0.0001) and had significantly larger abscess diameters (MD = 18.43&#xa0;mm, <i>P</i> &lt; 0.0001) than those in the success group. Furthermore, higher gravidity (MD = 0.59, <i>P</i> = 0.0001) and parity (MD = 0.32, <i>P</i> = 0.002) were identified as significant risk factors for treatment failure. No statistically significant associations were found between treatment failure and history of smoking, history of PID, intrauterine device use, palpable pelvic mass or positive pathogen culture.</p> Conclusion <p>Advanced age, larger abscess diameter and multiparity are potential risk factors for antibiotic treatment failure in TOA. For such high-risk patients, more aggressive monitoring or early combined minimally invasive drainage strategies are recommended.</p>