The Cellular Networks in Cancer (CNC) Program is a scientifically rich, collaborative, and productive research program co-led by Melanie Cobb, PhD, and Ralph DeBerardinis, MD, PhD. The vision of the CNC Program is to advance the fundamental knowledge of both intercellular and intracellular networks that contribute to cancer initiation, tumorigenesis, and metastasis, then to translate these findings into novel approaches to cancer prevention and therapy. CNC’s overarching scientific goal is to promote discoveries in how perturbation in these cellular networks contribute to altered tissue physiology and promote cancer. The CNC Program provides a highly interactive research environment that capitalizes on the UT Southwestern Medical Center’s (UTSW) longstanding tradition of basic science discoveries and fosters translation of these discoveries into the development of new biomarkers, diagnostic technologies, and therapeutic interventions in clinical oncology- especially malignancies relevant to the SCCC catchment area (e.g., cancer of the lung and kidney). The program’s structure is purposefully designed to stimulate interdisciplinary intra- and interprogrammatic collaborations with the objective of delivering transformative discoveries. To accomplish this, the Co-Leaders established four vibrant and synergistic subprograms that deliberately align with the strengths of program members and specifically relate to states of perturbed tissue homeostasis in cancer: (1) Signaling and Cell Biology, (2) Epigenetics and Gene Regulation, (3) Immunobiology, and (4) Metabolism. Each subprogram is directed by an investigator who is highly respected for his or her science, mentoring, and collaborative spirit. The subprogram structure and activities have directly contributed to exciting new collaborative projects such as the SPORE in Kidney Cancer. The CNC Program is composed of 59 basic, computational, and physician-scientists from 19 departments and centers at UT Southwestern Medical Center. Seven members of the CNC are Howard Hughes Medical Institute investigators. Annual direct peer-reviewed funding to the CNC Program was $19.3M in 2019. This represents an increase of $3.8M as compared with 2014 data, which were adjusted to conform to revised NCI guidelines. NCI funding has likewise increased from $3M in 2014 to $3.9M in 2019. Program members have authored 750 publications since 2014: 14% represent intraprogrammatic work, 34% are interprogrammatic collaborations, 32% are inter-institutional, and 37% are in journals with an impact factor ≥ 10. CNC Program members are heavily reliant upon all six CCSG Shared Resources—especially Live Cell Imaging and Tissue Management—in furtherance of their scientific goals. The CNC Program’s success is supported by SCCC’s strong infrastructure and grounded in the program’s solid interactions among CNC members and the subprograms, as well as with other SCCC Research Program members and external collaborators.