The tumor microenvironment is highly heterogeneous, containing not only primary cancer cells, but also stromal elements such as fibroblasts, lymphocytes, and macrophages. Due to this heterogeneity several tumor cells also pursue oxidative phosphorylation as a predominant energy source along with glycolysis. Changes in nutrient and oxygen availability within the tumor dictate glycolytic or oxidative phenotypes. This dynamic metabolic plasticity is also critical for sustaining the pentose phosphate pathway and tricarboxylic acid cycle intermediates for macromolecule and biomass generation for the rapidly growing tumor. Several recent literature reports also indicate that cancer cells initiate oxidative stress in the neighboring cancer associated fibroblasts, resulting in mitochondrial dysfunction and aerobic glycolysis. These fibroblasts then produce energy-rich metabolites (such as lactate and pyruvate) that are taken up by adjacent cancer cells for mitochondrial oxidative phosphorylation and further proliferation. In essence, the fibroblasts and cancer cells develop a strong metabolic symbiosis for energy generation.