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The current standard of care (platinum-based drugs) for the treatment of different forms of malignancy have been very effective in the clinic, however the negative side effects associated with the administration of these platinum based-drugs remains an unsolved problem. Gold based molecules are among a few metal complexes that have been developed over the years in search for better chemotherapy drugs. While the anticancer mechanism of action of platinum-based drugs is well known to involve DNA damage, the mechanism of action of gold based small molecules remains a subject of debate. It is understood that gold-based complexes exhibit non-cisplatin like anticancer mechanism of action, hence the potential to overcome resistance seen in patients with recurrent tumors after initial remission with platinum-based drugs. Herein, we report efforts to elucidate the mechanism of action of novel gold-based anticancer agents with very potent inhibitory effect against triple negative breast cancers and ovarian cancer. A recurring observation from the mechanism of action studies is the perturbation of mitochondria physiology by these complexes. These includes; perturbation of mitochondria bioenergetics, depolarization of mitochondria membrane potential of the cells, increased mitochondria ROS production, depletion of mitochondria DNA, and disruption of mitochondria dynamics. Modified versions of the lead molecules were developed as probes to monitor in vitro localization of the complexes and facilitate elucidation of the mechanism of action. Target identification studies with a biotinylated lead complex unveiled heme oxygenase 2 (HMOX2) as a novel target in gold medicinal chemistry. Preliminary target validation studies revealed for the first time, HMOX2 as an upstream regulator of the MYC proto-oncogene. These findings uncover a new strategy for targeting tumor cells and reinforces the belief that small molecules can serve as probes to interrogate the complex cancer biology system and unveil new strategies for development of better chemotherapeutic agents.