Triple negative breast cancer (TNBC) represents one of the most aggressive types of breast cancer, characterized by a high rate of metastasis and poor prognosis. Due to the lack of HER- 2, progesterone receptor and estrogen receptor, targeted therapies remain largely ineffective. Chemotherapy remains the standard of care despite poor outcome caused by mechanisms of resistance. In the present project, a High-Throughput Kinase Activity Mapping was conducted on TNBC cell lines treated with a panel of chemotherapies. This revealed that the MAP3K8 kinase is hyperactivated upon exposure to chemotherapeutic stress. Next, cell lines were transduced to overexpress MAP3K8. MAP3K8 overexpression increased cell proliferation and resistance to chemotherapy. Finally, to tackle drug resistance, multiple drug combinations were tested, and some showed improved outcome compared to individual chemotherapy treatment, including when using MAP3K8 inhibitors. We hope that these results may lead to the design of effective drug combination and eventually improve TNBC patients’ survival.