Cachexia is a devastating form of muscle wasting that is commonly associated with cancer. To understand the molecular basis of cachexia-associated muscle atrophy, Fukawa et al. carried out transcriptomic- and metabolomic-profiling analysis of human muscle stem cell-based models and human cancer-induced cachexia models in mice. This analysis revealed that cachectic cancer cells secrete inflammatory factors that induce muscle fatty acid oxidation (FAO), leading to oxidative stress, p38 mitogen-activated protein kinase (MAPK) activation and progressive muscle wasting. Inhibition of fatty acid-induced oxidative stress using etomoxir rescued weight loss and improved muscle mass in cachectic mouse models.