The placenta, an ancient organ with new functions, plays a crucial role in providing nutrients, gases, and hormones to the developing fetus. It also acts as an endocrine organ, orchestrates maternal adaptations during pregnancy, and acts as a selective barrier to protect the fetus from xenobiotics, pathogens, and parasites. Despite its central role in establishing a normal pregnancy, the placenta remains understudied. The transition from oviparity to viviparity and the establishment of feto-maternal communication introduced the placenta as the major anatomical site for these exchanges. The placenta undergoes complex developmental processes, including trophoectoderm differentiation, decidualization, and trophoblast invasion, which are regulated by various factors and signaling pathways. The placenta's immunomodulatory role is essential for maintaining a successful pregnancy. It modulates the endometrial immune system, allowing for immune tolerance to the fetus while preventing the vertical transmission of infectious agents. The placenta also expresses numerous proteins that are biomarkers for gestational diseases. Interestingly, placentation and carcinogenesis share many similarities, such as metabolism, cell behavior, molecular signatures, signaling pathways, and tissue microenvironment. This has led to the concept of "cancer as ectopic trophoblastic cells," suggesting that cancer may be a negative consequence of invasive placentation. Recent research has highlighted the potential of using placental-derived antigens for cancer therapy and immunotherapy. Placental heat shock protein, glycoprotein-96 (gp96), and other placental products have shown promise in reducing tumor volume and enhancing cytotoxicity in animal models. The placenta's unique properties and functions make it a promising target for future cancer research and treatment.The placenta, an ancient organ with new functions, plays a crucial role in providing nutrients, gases, and hormones to the developing fetus. It also acts as an endocrine organ, orchestrates maternal adaptations during pregnancy, and acts as a selective barrier to protect the fetus from xenobiotics, pathogens, and parasites. Despite its central role in establishing a normal pregnancy, the placenta remains understudied. The transition from oviparity to viviparity and the establishment of feto-maternal communication introduced the placenta as the major anatomical site for these exchanges. The placenta undergoes complex developmental processes, including trophoectoderm differentiation, decidualization, and trophoblast invasion, which are regulated by various factors and signaling pathways. The placenta's immunomodulatory role is essential for maintaining a successful pregnancy. It modulates the endometrial immune system, allowing for immune tolerance to the fetus while preventing the vertical transmission of infectious agents. The placenta also expresses numerous proteins that are biomarkers for gestational diseases. Interestingly, placentation and carcinogenesis share many similarities, such as metabolism, cell behavior, molecular signatures, signaling pathways, and tissue microenvironment. This has led to the concept of "cancer as ectopic trophoblastic cells," suggesting that cancer may be a negative consequence of invasive placentation. Recent research has highlighted the potential of using placental-derived antigens for cancer therapy and immunotherapy. Placental heat shock protein, glycoprotein-96 (gp96), and other placental products have shown promise in reducing tumor volume and enhancing cytotoxicity in animal models. The placenta's unique properties and functions make it a promising target for future cancer research and treatment.