INTRODUCTION: Apigenin, a widely distributed bioactive flavonoid, has recently gained excellent attention among researchers as an effective anticancer drug that can alternate cancer-signaling pathways, induce programmed cell death, and reduce tumor growth in various cancer types. Despite its impressive anti-neoplastic activity, high hydrophobicity, and nonspecific biodistribution make apigenin difficult for pharmaceutical applications. AREAS COVERED: We highlighted the therapeutic potential of apigenin and its derivatives in different cancer types, along with their mechanism of action. Nanoengineered drug delivery systems have remarkable applications in minimizing drug degradation and enhancing the therapeutic efficacy of drugs with sustained release, prolonged blood retention time, and reduced off-target toxicities. This review has evaluated and explored the molecular interactions of this novel flavonoid in various cancer signaling pathways to selectively inhibit neoplastic development in multiple cancer types. To ensure the complete coverage of the explored research area, Google Scholar, PubMed, and Web of Science were used to find not only the most relevant but also connected and similar articles. EXPERT OPINION: A comprehensive overview of apigenin nanotherapy in cancer treatment can establish a platform to overcome its difficulties for pharmaceutical applications and efficient clinical translation from bench to bedside.