Cancer treatment options are expanding to the benefit of significant segments of patients. However, their therapeutic power is not equally realized for all cancer patients due to drug toxicity and disease resistance. Overcoming these therapeutic challenges would require a better understanding of the adaptive survival mechanisms of cancer. In this respect, an integrated view of the disease as a complex adaptive system is proposed as a framework to explain the dynamic coupling between the various drivers underlying tumor growth and cancer resistance to therapy. In light of this system view of cancer, the immune system is in principal the most appropriate and naturally available therapeutic instrument that can thwart the adaptive survival mechanisms of cancer. In this respect, new cancer therapies should aim at restoring immunosurveillance by priming the induction of an effective immune response through a judicious targeting of immunosuppression, inflammation, and the tumor nutritional lifeline extended by the tumor microenvironment.