Triple Negative Breast Cancer (TNBC) is a complex malignancy subtype which commonly forms aggressive tumors with substantial stromal involvement. Unlike the Luminal and Her2+ breast cancer subtypes, TNBC tumors are unable to be targeted by highly specific therapies which exploit vulnerability in receptor expression to slow tumor growth. While some patients see initial benefit upon treatment with general or targeted chemotherapies, many patients relapse as their tumors adapt to the treatment and activate signaling pathways which allow them to survive therapy. In this, work I use an integrative experimental-computational approach to deeply profile TNBC tumor models during drug treatment and gain a mechanistic understanding of how transcriptional changes within malignant and stromal cells enable drug resistance.