Abstract: Cancer-related inflammation (CRI) plays a vital role in the development of cancer. Prostaglandin E2 (PGE2) is the most abundant eicosanoid lipid in the inflammatory environment and also a lipid metabolite with immunoregulatory functions in the tumor microenvironment. PGE2 synthetic pathway-blocking drugs combined with anti-tumor drugs have achieved good results in tumor treatment. Therefore, new directions and targets can be found for tumor prevention and treatment if regulatory links of the PGE2 synthesis pathway in the tumor microenvironment and mechanism of tumorigenesis and development are understood. Here, we summarize the research progress of PGE2 in tumorigenesis, development, and microenvironment remodeling in recent years.