The lack of recovery prospects in advanced cancer patients has often led to neglect important achievable therapeutic objectives, such as Quality of Life (QL) improvement, aimed at preserving, for as long as possible, patient integration with their family and social environment. In fact, traditional antineoplastic therapy protocols have been for a long time designed to demonstrate an advantage in clinical response and survival but have ignored essential supportive therapies and psychological and social well-being safeguard programs. Recent research of early integrated palliative care, including supportive care, aimed to obtain patient-centered therapeutic objectives. Noteworthy, advanced cancer patients often present a multiplicity of signs and symptoms responsible for physical impairment and reduction of functional abilities with consequent impossibility of carrying out the common daily activities. Additionally, the psycho-emotional integrity, the maintenance of family and social relationships and the spiritual issues contribute substantially to the optimal patients’ QL. Then, in the care of cancer patients their physical, psychological, social and spiritual needs should be globally addressed. In this context, cancer-related symptoms, which often occur in advanced stage cancer patients and can be either improved or worsened by the antineoplastic therapy, should be treated simultaneously with the planning and implementation of the most appropriate antineoplastic therapy. Therefore, any therapeutic approach should ideally be introduced within a context of the “best supportive care”, which includes optimal symptom management. To obtain this scope, the knowledge and awareness of the biological specificity of the disease and patient psychosocial interactions can no longer be considered optional by the multidisciplinary medical team in charge. To date, many of the mechanisms at the basis of the pathogenesis of many cancer-related symptoms are far from being fully understood. Consequently, an effective treatment is yet lacking and represent an unmet need in oncology clinical practice. This Research Topic includes articles in the field of biochemical, and molecular investigations, physiological and clinical studies related to the pathogenesis and potential targeted approaches of some important cancer signs and symptoms. We focused on cachexia, anorexia, muscle wasting, osteopenia, cancer-related anemia, physical inactivity and fatigue. The Research Topic includes Original Research, Review and Perspective articles.