BackgroundThere has been no systematic review and meta‐analysis to analyze and summarize the predictive factors of successful sperm extraction in salvage microdissection testicular sperm extraction.ObjectivesWe aimed to investigate the factors predicting the result of salvage microdissection testicular sperm extraction in patients with non‐obstructive azoospermia who failed the initial microdissection testicular sperm extraction or conventional testicular sperm extraction.Materials and methodsWe conducted a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library for literature that described the characteristics of patients with non‐obstructive azoospermia who underwent salvage microdissection testicular sperm extraction after failing the initial microdissection testicular sperm extraction or conventional testicular sperm extraction published prior to June 2022.ResultsThis meta‑analysis included four retrospective studies with 332 patients with non‐obstructive azoospermia who underwent a failed initial microdissection testicular sperm extraction and three retrospective studies with 177 non‐obstructive azoospermia patients who underwent a failed conventional testicular sperm extraction. The results were as follows: among non‐obstructive azoospermia patients whose first surgery was microdissection testicular sperm extraction, younger patients (standard mean difference: −0.28, 95% confidence interval [CI]: −0.55 to −0.01) and those with smaller bilateral testicular volume (standard mean difference: −0.55, 95% CI: −0.95 to −0.15), lower levels of follicle‐stimulating hormone (standard mean difference: −0.86, 95% CI: −1.18 to −0.54) and luteinizing hormone (standard mean difference: −0.68, 95% CI: −1.16 to −0.19), and whose testicular histological type was hypospermatogenesis (odds ratio: 3.52, 95% CI: 1.30–9.53) were more likely to retrieve spermatozoa successfully, while patients with Sertoli‐cell‐only syndrome (odds ratio: 0.41, 95% CI: 0.24–0.73) were more likely to fail again in salvage microdissection testicular sperm extraction. Additionally, in patients who underwent salvage microdissection testicular sperm extraction after a failed initial conventional testicular sperm extraction, those with testicular histological type of hypospermatogenesis (odds ratio: 30.35, 95% CI: 8.27–111.34) were more likely to be successful, while those with maturation arrest (odds ratio: 0.39, 95% CI: 0.18–0.83) rarely benefited.ConclusionWe found that age, testicular volume, follicle‐stimulating hormone, luteinizing hormone, hypospermatogenesis, Sertoli‐cell‐only syndrome, and maturation arrest were valuable predictors of salvage microdissection testicular sperm extraction, which will assist andrologists in clinical decision‐making and minimize unnecessary injury to patients.