A six-membered benzene ring is fused with a five-membered imidazole ring at positions four and five, generating benzimidazole, the benzo derivative of imidazole and a bicyclic aromatic chemical compound. Benzimidazole is a significant pharmacophore in a variety of physiologically active heterocyclic compounds due to its distinctive characteristics and structural framework. Because benzimidazole is both aromatic and heterocyclic, it interacts with a range of biological targets via metal ion interactions, π–π stacking, and hydrogen bonding. Its broad range of medicinal chemistry applications, such as anti-inflammatory, antiviral, antifungal, and anticancer therapies, is based on these interactions. Its significance in the development of potentially novel therapeutic pharmaceuticals is highlighted by the fact that its structural flexibility permits the synthesis of derivatives with targeted bioactivity. Derivatives of benzimidazole have garnered significant research interest as potential anticancer medications. These heterocyclic compounds exhibit a wide range of biological activities, such as DNA interaction, enzyme inhibition, and modulation of cellular pathways crucial to cancer development. Thus, to optimize their therapeutic potential, recent studies have focused on evaluating the structure–activity relationships (SAR) of benzimidazole derivatives. The main topics of this review are the current developments in the synthesis, anticancer activity, and SAR studies of benzimidazole derivatives, which will shed light on the increasing role they play in cancer therapies.