Cancers are heterogeneous multicellular systems whose states and growth are dependent upon reciprocal interactions between genetically altered ‘initiated’ cells and the dynamic microenvironments in which they exist. This Keystone Symposia conference titled Tumor Microenvironment: Identifying Drivers of Progression and Resistance will embrace tumor cell-intrinsic and -extrinsic communication programs that regulate neoplastic progression and systemic aspects of host response to cancer (aging, cachexia, obesity and tumor immunity) that impact disease progression and responses to therapy.  The program will feature presentations discussing innovative experimental and computational tools designed to probe the tumor microenvironment (TME) and their application to identify tumor vulnerabilities that may reveal new therapeutic targets or aid in patient stratification. The conference will also include a practical workshop (“data jamboree”) that will focus on application of analytical tools developed by the NCI Human Tumor Atlas Data (HTAN) to study the TME. The program has been designed to bring together scientists from across areas that often do not interact, ranging from cancer biologists and immunologists to computational and chemical biology researchers. The connections between inflammation and cancer are an important focus of the program, and as a result, this conference will be held jointly with the Keystone Symposia conference on Inflammation Resolution: Emerging Concepts, Mechanisms and Disease Insights. This pairing will enhance connections between immunologists and cancer researchers. Through shared keynote and joint scientific sessions, meals and poster sessions, participants will have an opportunity to network and share cross-disciplinary insights, encouraging innovative collaborations towards illuminating new biology and therapeutic avenues in these intersecting fields.