By investigating the glycolytic function of ENO1, we identified ENO1 as a specific metabolic target for GC and established a foundation for multitarget combination therapies involving the ENO1 signaling pathway, including those that target glycolysis, the two major tumor-promoting pathways, intracellular ATP pool regulation, and intracellular–extracellular lactate homeostasis. This evidence concerns the gene ENO1 and gastric cancer.