Normal cell development and prevention of tumor formation rely on the tumor-suppressor protein p53. This crucial protein is produced from the Tp53 gene, which encodes the p53 protein. The p53 protein plays a vital role in regulating cell growth, DNA repair, and apoptosis (programmed cell death), thereby maintaining the integrity of the genome and preventing the formation of tumors. Since p53 was discovered 43 years ago, many researchers have clarified its functions in the development of tumors. With the support of the protein p53 and targeted artificial intelligence modeling, it will be possible to detect cancer and tumor activity at an early stage. This will open up new research opportunities. In this review article, a comprehensive analysis was conducted on different machine learning techniques utilized in conjunction with the protein p53 to predict and speculate cancer. The study examined the types of data incorporated and evaluated the performance of these techniques. The aim was to provide a thorough understanding of the effectiveness of machine learning in predicting and speculating cancer using the protein p53.