Breast carcinomas are heterogeneous neoplasms of the mammary gland epithelial cells. They are categorized based on molecular features, namely expression of hormone receptors & tyrosine kinase receptor, HER2, and contribute to differential therapy responses. Despite advancements in therapeutics, breast cancer still poses a significant challenge, in particular when diagnosed in young pre-menopausal women. The majority of these neoplasms diagnosed in this age group belong to the molecular type triple-negative breast cancer and do not express the three cardinal receptors, namely, ER/PR & HER2. Further, these neoplasms initially respond to conventional cytotoxic chemotherapy drugs, but they recur with a more resistant & aggressive phenotype and have poor prognosis. Earlier studies, including ours, have shown that P21-activated kinase -1 (PAK1), a member of the group-1 PAK family, a serine-threonine kinase, intra-cellular signalling protein, is implicated in several cancer types and also found to be upregulated in TNBC clinical samples as compared to adjacent normal. In this study, we have shown how therapy targeting PAK1 with a cocktail approach of PAK1 inhibitors in combination with cytotoxic drugs could help combat this aggressive cancer occurring in young women. After a comprehensive synergistic cytotoxicity screening of all chemotherapeutic drugs in the current treatment regime of TNBC chemotherapy with PAK1 inhibitors, we summarised that drugs doxorubicin, paclitaxel, and methotrexate work best in synergy with Pak1 inhibitor NVS PAK1. Further, our data shows that this combinatorial approach effectively reduces metastatic tumor burden and improves disease prognosis.