The metabolism of cancer cells is quite different from that of normal cells, and the strong plasticity of cancer has resulted in slow progress in the field of targeting cancer metabolism therapy. Pyruvate kinase is a key enzyme in the cellular glycolytic pathway, catalyzing the conversion of phosphoenolpyruvate to pyruvate and the production of adenosine triphosphate. pyruvate kinase M2 isozyme (PKM2) not only can promote cancer cell proliferation and anabolism by enhancing the Warburg effect, but also can translocate to nucleus as a co-transcription factor and protein kinase to regulate gene transcription, playing an important role in tumorigenesis and development. This review focuses on the new breakthroughs of PKM2 on the Warburg effect, anabolism and tumor microenvironment, and briefly introduces the non-metabolic function of PKM2 and the latest progress in the clinical translation of PKM2-targeting small molecule drugs, providing new ideas for tumor therapy.