Thus, the role of PGC-1α in the management of both the mitochondrial dynamics/functionality and redox biology (i.e., upregulation of SOD2, Nrf2, and GSH)—beneficial or detrimental for the tumor progression—seems to be paradoxical; however, it reflects the tumor metabolic heterogeneity and new insights on the impact of the spatio-temporal tuning of fluctuations of mROS levels on cancer cell state need further investigations. This evidence concerns the gene SOD2 and neoplasm.