This edited volume discusses the complexity of tumor microenvironments during cancer development, progression and treatment. Each chapter presents a different mathematical model designed to investigate the interactions between tumor cells and the surrounding stroma and stromal cells. The topics covered in this book include the quantitative image analysis of a tumor microenvironment, the microenvironmental barriers in oxygen and drug delivery to tumors, the development of tumor microenvironmental niches and sanctuaries, intravenous transport of the circulating tumor cells, the role of the tumor microenvironment in chemotherapeutic interventions, the interactions between tumor cells, the extracellular matrix, the interstitial fluid, and the immune and stromal cells. Mathematical models discussed here embrace both continuous and agent-based approaches, as well as mathematical frameworks of solid mechanics, fluid dynamics and optimal control theory. The topics in each chapter will be of interest to a biological community wishing to apply the mathematical methods to interpret their experimental data, and to a biomathematical audience interested in exploring how mathematical models can be used to address complex questions in cancer biology.