Abstract Objectives Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing survival in patients with MF. The aim of this study was to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms. Methods We reported on a case of a patient with MF who presented with weight loss and cachexia associated with severe anemia, fatigue, fever, and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin, and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral l -carnitine, celecoxib, curcumin, lactoferrin, and subcutaneous recombinant human erythropoietin (EPO)-α. Results Surprisingly, after 1 y, cachexia features improved, all MF symptoms were in remission, and inflammatory and oxidative stress parameters, hepcidin, and EPO were reduced. Conclusions Because our protocol was targeted at inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and demonstrates a need for the study of new integrated therapeutic strategies.