 The dynamic interactions between cancer cells and their microenvironment, including stromal cells and extracellular matrix components, are crucial for the heterogeneity of cancer cells, clonal evolution, multidrug resistance, and progression to metastasis. These interactions force stromal cells to lose function, and acquire new phenotypes that promote tumor cell development and invasion. Understanding these mechanisms can inform the development of novel therapeutic strategies and diagnostic tools for cancer. This review focuses on advanced cancer models, including 3D systems and lab-on-chip devices. This article was authored by Rogeya Bagban, Leila Ross-Hanger, Rana Jahambanes Phalan, and others.