Alpha-fetoprotein (AFP), a major oncofetal protein, plays a pivotal role in cancer biology, extending beyond its initial identification in fetal development. Alpha-fetoprotein has multifaceted physiological functions mediated by its’ complex structure interacting with specific receptors and ligands. The involvement of AFP in carcinogenesis encompasses a broad spectrum of pathophysiological mechanisms, including cell proliferation, apoptosis, metastasis, and immune modulation. Alpha-fetoprotein contributes to the pathological landscape of several cancers, especially hepatocellular carcinoma and germ cell tumors, through an intricate network of signaling pathways. Recent studies highlight the expanding clinical applications of AFP, suggesting its potential to improve the diagnosis and treatment of cancer as well as monitoring genetic diseases, such as neural tube defects and Down syndrome. This comprehensive overview of AFP aims to elucidate the complex biological interactions and clinical implications in cancer management.