In this study, the authors propose a novel metabolic link between bladder cancer (BCa) cells and ECs in the nutrient‐scarce TME, in which BCa‐secreted glutamine‐fructose‐6‐phosphate aminotransferase 1 (GFAT1) via small extracellular vesicles (sEVs) reprograms glucose metabolism by increasing hexosamine biosynthesis pathway flux in ECs and thus enhances O‐GlcNAcylation. This evidence concerns the gene GFPT1 and urinary bladder cancer.