Altogether, this work reveals the unique role of the specific ECM-myCAF population and identifies G0S2 as a key player in chemoresistance in TNBC.<h4>Significance</h4>Integration of patient data with ex vivo tumor-on-chip modeling identifies an extracellular matrix-producing myofibroblast population that contributes to chemoresistance and can be targeted to improve outcomes in triple-negative breast cancer. The gene discussed is G0S2; the disease is triple-negative breast carcinoma.