Snakebite envenoming is a significant public health issue, causing mortality and severe morbidity. The toxins in snake venoms can be categorized into neurotoxicity, haemotoxicity, and tissue-damaging effects, with the latter including cytotoxicity and extracellular matrix (ECM) degradation. Traditional classification methods, such as cardiotoxins and myotoxins, are phenomenological and do not consider the mechanistic aspects of toxin action. This review proposes a new classification based on the mechanisms of action of cytotoxins, which can be direct or indirect. Direct cytotoxic effects are caused by cytotoxic three-finger toxins (3FTxs), phospholipase A2s (PLA2s), and β-defensin-like toxins, while indirect effects are mediated by snake venom metalloproteinases (SVMPs) and hyaluronidases degrading the ECM. These toxins can cause a range of pathological and pathophysiological effects, including local and systemic myonecrosis, demonecrosis, acute kidney injury, and chronic disabilities. The review discusses the clinical implications of these effects and potential therapeutic strategies, such as enzyme inhibitors and recombinant antibodies, to address the challenges of tissue damage in snakebite envenoming.Snakebite envenoming is a significant public health issue, causing mortality and severe morbidity. The toxins in snake venoms can be categorized into neurotoxicity, haemotoxicity, and tissue-damaging effects, with the latter including cytotoxicity and extracellular matrix (ECM) degradation. Traditional classification methods, such as cardiotoxins and myotoxins, are phenomenological and do not consider the mechanistic aspects of toxin action. This review proposes a new classification based on the mechanisms of action of cytotoxins, which can be direct or indirect. Direct cytotoxic effects are caused by cytotoxic three-finger toxins (3FTxs), phospholipase A2s (PLA2s), and β-defensin-like toxins, while indirect effects are mediated by snake venom metalloproteinases (SVMPs) and hyaluronidases degrading the ECM. These toxins can cause a range of pathological and pathophysiological effects, including local and systemic myonecrosis, demonecrosis, acute kidney injury, and chronic disabilities. The review discusses the clinical implications of these effects and potential therapeutic strategies, such as enzyme inhibitors and recombinant antibodies, to address the challenges of tissue damage in snakebite envenoming.