Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, lacking the expression of estrogen receptor, progesterone receptor, and HER2, which leads to poor prognosis and limited treatment options. Despite advances in targeted therapies, TNBC patients often fail to benefit due to its heterogeneity, drug resistance, and immune evasion. Gene editing technologies such as CRISPR/Cas9 and RNA interference offer promising strategies for precise gene modulation, yet their clinical translation is challenged by delivery efficiency, off-target effects, and safety concerns. This review systematically summarizes key regulatory genes implicated in TNBC progression, including those involved in invasion, proliferation, and chemoresistance, such as BRCA1/2, TP53, MUC1, EGFR, MYC, and others. We further discuss advances in gene editing tools and their combination with targeted delivery materials-ranging from viral vectors (AAV, lentivirus) to nonviral platforms (lipid nanoparticles, polymer-based systems, and bioderived vesicles)-highlighting their potential to enhance editing specificity, minimize immune response, and overcome tumor microenvironment barriers. Finally, we address biosafety, ethical concerns, and mitigation strategies such as high-fidelity Cas9 variants and AI-assisted off-target prediction. Collectively, this review provides a comprehensive framework for future research and clinical application of targeted gene editing in TNBC, aiming to develop safer, more effective, and personalized treatment strategies.