Abstract: Short-term stress positively affects homeostasis recovery; however, long-term stress leads to various dis-eases. Accumulating evidence shows that cancer processes are not only related to genetics and environ-ment but also to chronic stress. For patients with cancer, the disease process induces prolonged psychological and physical stress, including fear and pain, which makes chronic stress common in patients. Chronic stress, in turn, regulates different components of the primary tumor and tumor microenvironment through a wide variety of stress mediators. Furthermore, studies indicate that chronic stress increases tumor burden and mortality in patients with different types of cancer, while the management of chronic stress can alleviate disease burden and extend patient survival. Therefore,a deeper understanding of the role and mechanism of chronic stress in cancer is necessary for developing new strategies for cancer treatment beyond traditional treatment approaches.Herein, we explored the different sources of chronic stress, the molecular mechanisms through which chronic stress affects cancer development and progression, and the stress mediators involved. We discussed the multiple impacts of chronic stress on cancer, as well as the currently available intervention strategies. We also highlighted the prospects and challenges of chronic stress management in the clinical treatment of cancer.