p53 is a crucial tumor suppressor that responds to various stress signals by orchestrating cellular responses such as cell cycle arrest, senescence, and apoptosis, all of which contribute to tumor suppression. Recent studies have challenged the importance of these classical responses and highlighted other roles of p53 in metabolism, stem cell maintenance, invasion, metastasis, and tumor microenvironment communication. This review discusses both classical and emerging p53 functions in tumor suppression. p53 is essential for tumor suppression, as its inactivation is common in many cancers, and individuals with Li-Fraumeni syndrome, who inherit a mutant TP53 allele, are prone to cancer. During tumor development, TP53 mutations often lead to loss of heterozygosity, resulting in complete p53 deficiency. p53 deficiency can enhance cancer initiation or progression, and tumors lacking p53 are often more malignant, characterized by poor differentiation, genetic instability, and increased invasiveness. p53 is a member of a family of transcription factors, including p63 and p73, and these factors have overlapping and distinct roles. p53 acts as a stress sensor, triggering cell cycle arrest, senescence, and apoptosis in response to various stresses. It is displaced from its negative regulators MDM2 and MDM4, allowing its stabilization and activation. p53 is involved in various processes, including metabolism, stem cell function, invasion, and metastasis, which may also contribute to tumor suppression. Studies using mouse models have shown that p53 deficiency leads to various tumors, highlighting its importance in tumor suppression. p53's role in tumor suppression is also evident in its ability to induce cell cycle arrest, senescence, and apoptosis. However, recent studies suggest that p53's tumor suppressor function may not rely solely on these classical responses but also on other functions, such as regulating metabolism. p53's ability to regulate metabolism is crucial for tumor suppression. It opposes oncogenic metabolic reprogramming by stimulating oxidative phosphorylation and inhibiting glycolysis. p53 also limits ROS accumulation, which is essential for maintaining cellular integrity and preventing neoplasia. Additionally, p53 can induce autophagy, which helps in tumor suppression by promoting apoptosis and limiting ROS accumulation. p53 also plays a role in regulating stem cells, inhibiting their self-renewal and promoting differentiation. This function is important for preventing the development of tumorigenic stem cells. p53 can also impose a barrier to invasion and metastasis by opposing epithelial-to-mesenchymal transition (EMT), a process associated with cancer progression. Furthermore, p53 has non-cell-autonomous functions in the tumor microenvironment, influencing the behavior of surrounding cells and promoting an anti-tumorigenic environment. p53 can stimulate the recruitment of immune cells and modulate the tumor stroma, which is crucial for tumorp53 is a crucial tumor suppressor that responds to various stress signals by orchestrating cellular responses such as cell cycle arrest, senescence, and apoptosis, all of which contribute to tumor suppression. Recent studies have challenged the importance of these classical responses and highlighted other roles of p53 in metabolism, stem cell maintenance, invasion, metastasis, and tumor microenvironment communication. This review discusses both classical and emerging p53 functions in tumor suppression. p53 is essential for tumor suppression, as its inactivation is common in many cancers, and individuals with Li-Fraumeni syndrome, who inherit a mutant TP53 allele, are prone to cancer. During tumor development, TP53 mutations often lead to loss of heterozygosity, resulting in complete p53 deficiency. p53 deficiency can enhance cancer initiation or progression, and tumors lacking p53 are often more malignant, characterized by poor differentiation, genetic instability, and increased invasiveness. p53 is a member of a family of transcription factors, including p63 and p73, and these factors have overlapping and distinct roles. p53 acts as a stress sensor, triggering cell cycle arrest, senescence, and apoptosis in response to various stresses. It is displaced from its negative regulators MDM2 and MDM4, allowing its stabilization and activation. p53 is involved in various processes, including metabolism, stem cell function, invasion, and metastasis, which may also contribute to tumor suppression. Studies using mouse models have shown that p53 deficiency leads to various tumors, highlighting its importance in tumor suppression. p53's role in tumor suppression is also evident in its ability to induce cell cycle arrest, senescence, and apoptosis. However, recent studies suggest that p53's tumor suppressor function may not rely solely on these classical responses but also on other functions, such as regulating metabolism. p53's ability to regulate metabolism is crucial for tumor suppression. It opposes oncogenic metabolic reprogramming by stimulating oxidative phosphorylation and inhibiting glycolysis. p53 also limits ROS accumulation, which is essential for maintaining cellular integrity and preventing neoplasia. Additionally, p53 can induce autophagy, which helps in tumor suppression by promoting apoptosis and limiting ROS accumulation. p53 also plays a role in regulating stem cells, inhibiting their self-renewal and promoting differentiation. This function is important for preventing the development of tumorigenic stem cells. p53 can also impose a barrier to invasion and metastasis by opposing epithelial-to-mesenchymal transition (EMT), a process associated with cancer progression. Furthermore, p53 has non-cell-autonomous functions in the tumor microenvironment, influencing the behavior of surrounding cells and promoting an anti-tumorigenic environment. p53 can stimulate the recruitment of immune cells and modulate the tumor stroma, which is crucial for tumor