Various in vitro and in vivo studies show that targeting heme and mitochondrial respiration using heme sequestration molecules, HO-1 inhibitor, mitochondrial respiration inhibitor, and inhibitor of OXPHOS complexes could improve hypoxia, normalize vasculature, reduce oxygen consumption of cancer cells, and ultimately restore immunosupportive TME and anti-tumor immunity. This evidence concerns the gene HMOX1 and cancer.