Purpose Neoadjuvant therapy (NAT) in breast cancer enables tumor downstaging and response evaluation. Although magnetic resonance imaging (MRI) is the gold standard, its limitations have prompted growing interest in alternatives such as contrast-enhanced mammography (CEM). Methods This review was conducted according to PRISMA guidelines. We evaluated CEM accuracy in predicting pathological complete response after NAT, using surgery as reference standard. A comprehensive search was conducted in PubMed/Medline, Embase, Cochrane, and Web of Science. Two reviewers screened studies, extracted data, and evaluated risk of bias with QUADAS-2 tool. A bivariate random-effects model estimated diagnostic odds ratio (DOR), sensitivity, specificity, and likelihood ratios. Summary receiver operating characteristic (sROC) curves were generated, and heterogeneity was quantified using Higgins’ I ² . Publication bias was assessed via Deek’s funnel plot. Results Fifteen studies, including 793 patients, met inclusion criteria. The pooled analysis showed a DOR of 9.30 (95% CI 4.15–20.83) with substantial heterogeneity (I ² = 72.30%). Pooled sensitivity and specificity were 74% (95% CI 66%–81%) and 82% (95% CI 67%–91%), respectively, with an sROC AUC of 0.83 (95%, CI 0.67–0.92). Excluding the study contributing most to heterogeneity improved the DOR to 10.28 (95% CI 6.35–16.65) and reduced I ² to 19.4% ( p = 0.242). Conclusions CEM demonstrates good diagnostic accuracy for assessing NAT response, performing comparably to MRI. Trial registration This systematic review is registered in PROSPERO under the registration number CRD420251003406.