Systemic diseases, such as cancer, require thorough understanding not only of the properties that malignant cells have acquired through mutations but also the effects of the activity of these cells on the dynamic microenvironment of the host’s tissue. From this perspective, one can think of tumor cells as being hosted by tumor endothelial cells within the larger “ecosystem” of the human body. And just like in other ecosystems, the survival of tumor cells depends both on the state of the entire ecosystem and on the state of their immediate host. The focus of this research lies in using conceptual, biologically grounded mathematical models to applying the insights obtained from extensive studies of other ecosystems to the new information continuously being reported in the field of cancer biology. The goal of this work is to structure and advance the theoretical understanding of cancer as an evolving ecological system.