The tumor microenvironment (TME) consists of a complex assortment of multiple cell types and dynamic extracellular matrices. Model systems that mimic aspects of the TME are useful tools for probing signal transduction underlying progression. In this presentation I will demonstrate how mimicking the biophysical and biochemical attributes of the TME in spatially addressable assays can be used to better probe cancer processes. Hydrogel micropatterning can be used to coordinate the interactions of cancer cells and stroma, where confinement on deformable substrates triggers partitioning of different cell types in ways that mimic organisation in vivo. Regions of perimeter curvature are shown to activate fibroblasts to a contractile state, thereby leading to enhanced matrix deposition and corralling of cancer cells to the center. Using a geometric templating approach brings these assays into 3D, with the possibility of directing bi-directional cross talk with spatiotemporal control. Leveraging biofabrication can further increase the complexity by allowing cancer spheroids, stromal cells and vessel structures to be integrated within a single system. The fabrication of multiple aspects of the TME allows better control over features responsible for progression, thereby providing improved tools for fundamental studies and drug development.