Ewing’s sarcoma is the second most common malignant primary bone tumor in children and adolescents, marked by its exceptional malignancy, abbreviated patient course, and rapid metastasis, posing a substantial threat to the health of children and adolescents. Tumor cells promote metabolic reprogramming of nutrients including sugars, amino acids, lipids, and more through a series of complex regulatory mechanisms, thus maintaining the high metabolic state of tumor and promoting tumor development. The products related to metabolic reprogramming exert a significant impact on various cellular constituents in the tumor microenvironment, inhibiting anti-tumor immune responses, and even inducing drug resistance events. A pivotal player in this context is the Ewing sarcoma breakpoint region 1 (EWSR1)-Friend leukemia virus integration 1 (FLI1) fusion protein, which assumes multifaceted roles with intricate regulatory mechanisms. Understanding the specific metabolic changes and regulatory pathways orchestrated by EWSR1-FLI1 in Ewing’s sarcoma cells holds the promise of shedding light on the disease’s etiology. Additionally, this knowledge offers a path to the discovery of novel diagnostic and therapeutic markers and strategies. This article summarizes and analyzes the recent research progress of EWSR1-FLI1 on metabolic reprogramming in Ewing’s sarcoma, providing new ideas for the early diagnosis and precise treatment of the disease.