Glycolytic reprogramming is emerging as a hallmark of various cancers and a promising therapeutic target. Nanotechnology is revolutionizing the anti-tumor therapeutic approaches associated with glycolysis. Finely controlled chemical composition and nanostructure provide nanomaterials unique advantages, enabling an excellent platform for integrated drug delivery, biochemical modulation and combination therapy. Recent studies have shown promising potential of nanotherapeutic strategies in modulating tumor glycolytic metabolism alone or in combination with other treatments such as chemotherapy, radiotherapy and immunotherapy. To foster more innovation in this cutting-edge and interdisciplinary field, this review summarizes recent understandings of the origin and development of tumor glycolysis, then provides the latest advances in how nanomaterials modulate tumor glycolysis-related metabolism. The interplay of nanochemistry, metabolism and immunity is highlighted. Ultimately, the challenges and opportunities are presented.