Simple SummaryTriple-negative breast cancer (TNBC), the most aggressive and heterogenous type of cancer, lacks the expression of hormones like estrogen, progesterone, and human epidermal growth receptor-2, making chemotherapy the only treatment regimen against TNBC. It was further observed that chemotherapy leads to off-site toxicity and chemoresistance, decreasing anticancer activity. Therefore, to overcome the problem faced during chemotherapy, and to address the heterogeneity of TNBC, targeted therapy emerged based on the molecular profiling of TNBC. Such a scenario further encouraged the acceptance of biomarkers as some of the targeting moieties for effective and precise TNBC therapy. Several biomarkers are used as targets for the precision therapy in TNBC, including EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc. Additionally, nanoparticles were employed as parts of a multifunctional platform to deliver the therapeutics to the target site with increased precision.AbstractBreast cancer is a heterogeneous disease which accounts globally for approximately 1 million new cases annually, wherein more than 200,000 of these cases turn out to be cases of triple-negative breast cancer (TNBC). TNBC is an aggressive and rare breast cancer subtype that accounts for 10–15% of all breast cancer cases. Chemotherapy remains the only therapy regimen against TNBC. However, the emergence of innate or acquired chemoresistance has hindered the chemotherapy used to treat TNBC. The data obtained from molecular technologies have recognized TNBC with various gene profiling and mutation settings that have helped establish and develop targeted therapies. New therapeutic strategies based on the targeted delivery of therapeutics have relied on the application of biomarkers derived from the molecular profiling of TNBC patients. Several biomarkers have been found that are targets for the precision therapy in TNBC, such as EGFR, VGFR, TP53, interleukins, insulin-like growth factor binding proteins, c-MET, androgen receptor, BRCA1, glucocorticoid, PTEN, ALDH1, etc. This review discusses the various candidate biomarkers identified in the treatment of TNBC along with the evidence supporting their use. It was established that nanoparticles had been considered a multifunctional system for delivering therapeutics to target sites with increased precision. Here, we also discuss the role of biomarkers in nanotechnology translation in TNBC therapy and management.