Cell death pathways are critical for maintaining tissue homeostasis and are often dysregulated in cancer. Understanding these pathways provides insights into potential therapeutic strategies. This review explores key cell death mechanisms, including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, and their roles in cancer. The review emphasizes the importance of targeting these pathways to overcome drug resistance and improve cancer therapy. It discusses molecular mechanisms, signaling pathways, and the tumor microenvironment (TME) in regulating cell death. Key factors include the PI3K/AKT/mTOR, MAPK/ERK, and NF-κB pathways, which are crucial for cell survival and death. The TME, with its hypoxic and nutrient-deprived conditions, influences cancer cell behavior and therapy response. Therapeutic approaches include BH3 mimetics, death receptor agonists, necroptosis modulators, and agents targeting ferroptosis and pyroptosis. These strategies aim to selectively induce cell death in cancer cells while minimizing damage to normal tissues. The review highlights the potential of these approaches in developing more effective and targeted cancer therapies.Cell death pathways are critical for maintaining tissue homeostasis and are often dysregulated in cancer. Understanding these pathways provides insights into potential therapeutic strategies. This review explores key cell death mechanisms, including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, and their roles in cancer. The review emphasizes the importance of targeting these pathways to overcome drug resistance and improve cancer therapy. It discusses molecular mechanisms, signaling pathways, and the tumor microenvironment (TME) in regulating cell death. Key factors include the PI3K/AKT/mTOR, MAPK/ERK, and NF-κB pathways, which are crucial for cell survival and death. The TME, with its hypoxic and nutrient-deprived conditions, influences cancer cell behavior and therapy response. Therapeutic approaches include BH3 mimetics, death receptor agonists, necroptosis modulators, and agents targeting ferroptosis and pyroptosis. These strategies aim to selectively induce cell death in cancer cells while minimizing damage to normal tissues. The review highlights the potential of these approaches in developing more effective and targeted cancer therapies.