Stress is one of the fundamental survival mechanisms in nature. Although chronic or long-lasting stress can be detrimental to health, acute or short-term stress can have health benefits. The aim of the present review was to address the complexity and significance of stress in tumorigenesis. The review covers an evaluation of previously used and reported experimental animal models of stress, as well as the effects of stress on the neuroendocrine system, immune function, gut microbiota, and inflammation and multidrug resistance, all of which are closely associated with cancer occurrence, progression and treatment. The review concludes that understanding the efficacy of stress management (prevention and rehabilitation) is crucial to the development of comprehensive and individualized strategies for cancer prevention and treatment.