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Background: Breast cancer remains one of the leading causes of cancer-related morbidity and mortality among women worldwide, and survival outcomes are strongly associated with early detection. Although mammography has substantially improved screening outcomes, its diagnostic sensitivity may be limited in certain populations, particularly among women with dense breast tissue, highlighting the need for complementary diagnostic approaches. Blood-based molecular biomarkers have emerged as promising non-invasive tools capable of detecting tumor-associated biological signals at early stages of disease development. Objective: To systematically evaluate and synthesize available evidence on the diagnostic accuracy of blood-based molecular biomarkers for the early detection of breast cancer. Methods: A systematic review and diagnostic test accuracy meta-analysis were conducted following PRISMA guidelines. Electronic databases including PubMed, Scopus, Web of Science, and Embase were searched for studies published between 2000 and 2025. Eligible studies evaluated circulating molecular biomarkers in blood samples from women with early-stage breast cancer and reported sufficient data to calculate diagnostic accuracy. Study quality was assessed using the QUADAS-2 tool. Pooled sensitivity, specificity, and summary receiver operating characteristic (SROC) curves were calculated using a bivariate random-effects model. Results: Sixty-two studies involving 8,465 breast cancer cases and 8,045 controls were included. cfDNA fragment omics demonstrated the highest diagnostic accuracy (sensitivity 0.88, specificity 0.90, AUC 0.93), followed by cfDNA methylation markers (sensitivity 0.84, specificity 0.87, AUC 0.91). Circulating microRNA panels showed moderate-to-high performance (sensitivity 0.81, specificity 0.83, AUC 0.88), whereas traditional protein markers showed lower accuracy (sensitivity 0.62, specificity 0.68, AUC 0.70). Multi-marker panels consistently outperformed single biomarkers. Conclusion: Blood-based molecular biomarkers, particularly cfDNA fragment omics and methylation profiling, demonstrate strong potential as complementary tools for early breast cancer detection. However, further prospective screening studies and methodological standardization are required before routine clinical implementation.