In this presentation, current concepts on the formulation of a multimodal therapeutic plan to maintain patient fitness during treatment are discussed. In the setting of locally advanced / metastatic disease, patients are typically of older age, and often affected by malnutrition, sarcopenia, deconditioning/reduced physical functioning, comorbid conditions, and inflammation. Furthermore, systemic therapy, including cytotoxic, targeted and immunotherapies, have both a direct and indirect role to exacerbate malnutrition, and wasting of muscle and adipose tissues. Concordant with the understanding of the complex nature of the patients affected by cancer of advanced stage, multimodal intervention and the engagement of a multi-professional team are suggested to manage symptoms and side effects, and to maintain patient fitness, functional independence and tolerance of therapy. Elements of these interventions include various combinations of symptom management (e.g., counteract effects of systemic therapy such as nausea, palliative consultation), anti-inflammatory therapy (e.g. ibuprofen, celecoxib, omega 3-fatty acid), consultation with a nutrition health care professional, Medical Foods (i.e., foods specifically formulated and intended for the dietary management of a disease that has distinctive nutritional needs), exercise therapy (to develop strength, aerobic fitness, enable anabolism), and drug treatments (e.g. ghrelin – receptor agonists to restore appetite). Multimodal therapies have been tested for feasibility (e.g., NCT04575831) or are currently being tested in randomized clinical trials (e.g., NCT02330926). Multidisciplinary model of care have been reported (e.g. PMID 32751451, 24311946) and these show promising signs of clinical benefit.