Microenvironmental conditions contribute to the pathogenesis of cancer and include altered cellular composition, extracellular matrix (ECM) deposition, and mechanical cues. However, our understanding of the specific mechanisms by which these microenvironmental perturbations impact the development, progression, and therapy response of cancer is relatively limited. More intricate models are needed to better understand the complex biochemical and biophysical interactions that drive tumor initiation, growth, metastasis, metabolic adaptation, and immune evasion. The fields of biomaterials and tissue engineering provide increasingly sophisticated tools and strategies to recapitulate and monitor relevant properties of tumor-microenvironment interactions. These approaches not only bear tremendous potential to advance our current understanding of cancer, but are also increasingly explored for more clinically relevant drug testing. Indeed, combining patient-specific cells with engineered culture systems promises to enhance the predictive power of precision medicine pipelines. This talk will highlight specific examples of how the microenvironment regulates the highly dynamic nature of cancer and will outline opportunities and challenges of the field of tumor engineering.