Modifiable lifestyle factors are the strongest determinants and major preventable causes of most type of cancer. Exercise has shown many beneficial effects in cancer prevention and anticancer treatment. However, the underlying mechanisms remain unclear. To contribute to our understanding of the role of exercise regulation in cancer and provide recommendations for future preclinical and clinical exercise oncology research, we examine the functions of exercise in cancer and its underlying mechanisms. In addition to reducing the incidence of cancer, exercise can enhance the efficacy of certain types of approved anticancer treatments (e.g., targeted therapy, immunotherapy, and radiotherapy) and reduce the symptoms/side effects of cancer and its treatment (e.g., fatigue, cancer cachexia, cognitive impairment, and depression). The mechanisms mediating these effects include the regulation of intratumoral angiogenesis, myokines, adipokines and their associated pathways, cancer metabolism, and anticancer immunity. Cancer rehabilitation guidelines advise cancer survivors to perform exercises. Many ongoing clinical trials have investigated the effects and mechanisms of exercise in cancer. This review supports the prescription of exercise for cancer prevention to sensitize cancer to anticancer therapy and manage associated symptoms and side effects after cancer diagnosis.Copyright © 2022 Elsevier B.V. All rights reserved.