Despite emerging evidence that distress and adversity can contribute to negative health outcomes in cancer, little is known about the brain networks, regions, or circuits that can contribute to individual differences in affect/distress states and health outcomes in treated cancer patients. To understand the state-of-the-science in this regard, we reviewed neuroimaging studies with cancer patients that examined the associations between negative affect (distress) and changes in the metabolism or structure of brain regions. Cancer patients showed changes in function and/or structure of key brain regions such as the prefrontal cortex, thalamus, amygdala, hippocampus, cingulate cortex (mainly subgenual area), hypothalamus, basal ganglia (striatum and caudate), and insula, which are associated with greater anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, and distress. These results provide insights for understanding the effects of these psychological and emotional factors on peripheral stress-related biobehavioral pathways known to contribute to cancer progression and long-term health outcomes. This line of work provides leads for understanding the brain-mediated mechanisms that may explain the health effects of psychosocial interventions in cancer patients and survivors. A multilevel and integrated model for distress management intervention effects on psychological adaptation, biobehavioral processes, cancer pathogenesis, and clinical outcomes is proposed for future research.