This dataset presents a comparative proteomic analysis of the human fibrosarcoma cell line HT-1080 in response to treatment with nitrogen-doped graphene acid (NGA) and the single atom engineered derivatives, NGA-Fe3+ and NGA-Cu2+. To further investigate the role of metal-induced cell death pathways, cells were exposed to elesclomol, a well-known copper ionophore, and RSL3, a ferroptosis activating compound. The main objective was to characterize the proteomic alterations associated with single atom engineered NGA to elucidate potential mechanisms of action. We also examined the effects of elesclomol and RSL3 to provide reference datasets for copper-induced cytotoxicity (aka cuproptosis) and ferroptosis, respectively. This dataset provides insights into the cellular responses triggered by NGA and its derivatives and how these materials impinge on regulated cell death pathways.