There have been numerous efforts to develop targeted therapies for treating cancer. The non-specificity of 'classical' cytotoxic chemotherapy drugs and drug resistance remain major challenges in cancer dormancy. Mitochondria-targeted therapy is an alternative strategy for the treatment of numerous cancer types and is heavily dependent on the ability of the anticancer drugs to reach the tumor mitochondria in a safe and selective manner. Over the past two decades, research efforts have provided mechanistic insights into the roles of mitochondria in cancer progression and therapies that specifically target cancer mitochondria. Given that several nanotechnology-driven strategies aimed at therapeutically targeting mitochondrial dysfunction are still in their infancy, this review considers the cross-disciplinary nature of this area and focuses on the design and development of mitochondria-targeted graphene (mitoGRAPH), its immense potential, and future use for selective targeting of cancer mitochondria. This review also provides novel insights into the strategies for preparing mitoGRAPH to destroy the cell powerhouse in a targeted fashion. Targeting mitochondria with graphene may represent an important therapeutic approach that transforms therapeutic interventions. STATEMENT OF SIGNIFICANCE: Mitochondria-targeted therapy represents a major advance for treating several medical conditions. At this time, no nanoparticles (NPs) or nanocarriers are clinically available, which are capable of spatial targeting and controlled delivery of drugs to mitochondria. NPs-based approaches have revolutionized the field of targeted therapy and have demonstrated efficacy for delivering drugs selectively to mitochondria. These NPs show limited results in pre-clinical animal models due to their adverse side effects and inadequate therapeutic outcomes. Over the past decade, graphene has emerged as a potential anticancer agent and has shown great potential in targeting tumor mitochondria in a safe and targeted fashion. This review considers recent advances in the use of mitochondria-targeted graphene (mitoGRAPH) in chemotherapy, photodynamic therapy, photothermal therapy, and combination therapies.