Despite decades of research to develop new treatments for cancer, the current arsenal is ineffective for some patients. While some patients will achieve total remission, other cases will only see temporary tumor suppression or no effect at all. Failure to cure cancer patients will result in over 600,000 cancer-related deaths this year in the United States alone. Understanding the mechanisms which drive cancer growth, invasion, and drug resistance will prove invaluable for the development of next-generation cancer treatments. Unfortunately, this research is limited by the lack of model systems which encompass the heterogeneity of cancer in immune competent microenvironments. Engineered model systems have emerged as a solution to this problem. In this thesis, I present work utilizing various engineered models of the tumor immune microenvironment for validating drug response, characterizing macrophage phenotype modulation due to tumor-associated collagen, and investigating the effects of diet induced obesity on tumor immunity. These works highlight the broad application of engineered model systems for cancer research and suggest potential therapeutic targets for taming the disease in humans.