 The TP53 tumor suppressor gene is one of the most frequently altered genes in cancer and is known to play a crucial role in regulating cell growth, death and DNA repair. It is also involved in many other processes such as metabolism, autophagy and the tumor micro environment. Mutations in this gene are often found in cancer cells, leading to the loss of its tumor suppressor activity and the acquisition of oncogenic properties. Despite these findings, there has been limited success in developing effective treatment against cancer based on targeting the P53 protein or its downstream targets. This review summarizes the current understanding of the diverse molecular mechanisms of the P53 signaling pathway and how TP53 mutations affect tumor progression. Additionally, it discusses the challenges faced in clinical development of P53 targeted therapies.