Cytotoxin (CTX) is a highly basic three-finger toxin that exists predominantly in the cobra venom. However, its cytotoxicity may not be due to direct lytic action as few contradictory explanations have been proposed, while its molecular target is unknown. The current study examined the mechanisms of cytotoxicity and putative target death receptors of CTX derived from Naja sumatrana venom, using experimental and ensemble approaches. Cell-based apoptotic, membrane permeabilization assays, and label-free quantitative (LFQ) proteomics were used to examine cytotoxicity. The potential target death receptor was determined using an ensemble-based virtual screening and receptor-binding assay. At low toxin concentrations, CTX was found to cause caspase-dependent mitochondrial-mediated apoptosis. The absence of a necrosis marker, high mobility group box 1 (HMGB1), further confirmed that apoptosis was the leading cause of cell death. Nonetheless, the degree of membrane permeabilization increased with increasing toxin concentrations. This is associated with the occurrence of necroptosis, as demonstrated by LFQ proteomics. Necroptosis is presumably the initial stress response after exposure to high levels of toxins. In addition, the ensemble-based virtual screening of different death receptors revealed that tumor necrosis factor receptor 1 (TFNR1) is a potential target of CTX. The receptor’s binding sites interact with the three functional loops of CTX through hydrogen bonding and van der Waals forces. This was further validated by the TNFR1 receptor binding assay. Our findings showed that CTX triggered a concentration-dependent transition of apoptosis to necroptosis by CTX. This can be attributed to its direct interaction with TNFR1.