Cancer patients experience multiple symptoms throughout their illness trajectory. Symptoms consistently occurring together, known as symptom clusters, share common pathophysiologic mechanisms. Understanding and targeting such symptom clusters may allow for more effective and efficient use of treatments for a variety of symptoms. Fatigue-anorexia-cachexia is one of the most prevalent symptom clusters and significantly impairs quality of life. In this review, we explore the fatigue-anorexia-cachexia symptom cluster and focus on current and emerging therapies with an emphasis on pharmacologic management.