Cancer cells are excellent adapters and influencers, and as they grow and circulate through the body, they embed themselves in different niches, causing metastatic tumors. Certain niches, such as soft organs, seem to be preferentially chosen by metastatic cancer cells as favorable homes. Our study investigates how the physical properties of the tumor microenvironment could be conducive in promoting cancer stem cell formation and metastasis in certain niches. Cancer stem cells are considered responsible for micro-metastasis in distant organs which evade early detection, leading to recurrence and relapse. One of the ways we are exploring this is by varying the stiffness and pore alignment of 3D collagen scaffolds to replicate the mechanical heterogeneity seen across bone and tumor lesions. This image, captured through the ESEM (environmental scanning electron microscope), shows osteosarcoma cells growing within a mineralized collagen scaffold. So far, our study has shown evidence that osteosarcoma cells grown on a softer scaffold change into a more stem cell-like phenotype. By using variations of these 3D models, we aim to dissect the biomechanical crosstalk between the physical microenvironment and cancer cells to understand why cancer cells migrate to certain sites within the body and how they adapt.