Metabolic dysregulation in PH beyond the Warburg effect includes alterations in the pentose phosphate pathway (PPP), glutaminolysis, and FA handling; in certain contexts, it may include an increase of oxidative phosphorylation (a reverse of the Warburg effect); increased reliance on metabolic activities of HIF-2α and ROS signaling; and profound alterations of iron metabolism. Perturbations in mitochondrial dynamics involve altered mitochondrial biogenesis as well as increased fission and decreased fusion. Dysregulated mitochondrial mass and fragmentation result in metabolic reprogramming and tissue-specific dysfunction typical of PH. A more precise understanding of the complex molecular drivers of PH will inform novel diagnostic technologies and mitochondria-specific therapies. Development of imaging tools such as PET (image courtesy of J. Latoche and C. Anderson, In Vivo Imaging Facility at Hillman Cancer Center, UPMC) and cardiac MRI, high-throughput metabolomic analysis, as well as potential metabolic targeted therapies will be facilitated by a more granular understanding of mitochondrial pathology. Advancements in molecular and translational research may ultimately allow for a redefinition of PH subtypes through the lens of metabolic dysfunction, with great utility in strategizing appropriate precision medicine therapies. The processes by which other mitochondrial and metabolically driven diseases may be related to PH are yet to be determined. ETC, electron transport chain; HRE, hypoxia-response element.