Tumor stroma is characterized by the presence of a large number of cancer associated fibroblasts, macrophages, endothelial cells, and other immune cells. These cells are often present in aberrantly high numbers in tumor microenvironment that are distinctly different from normal cells. Targeting stroma cells proves a unique opportunity for cancer imaging and therapy. We have exploited the use of nanoparticles and imaging probes directed at cancer associated fibroblasts and macrophages for imaging therapy-induced cell death, assessing host response to tumor progression and suppression, and potentiation of conventional chemoradiotherapy. These work will be presented and discussed in the context of pancreatic cancer and ovarian cancer, and inflammatory diseases in my talk.