Imidazoles, indoles, and pyrimidines are promising heterocyclic scaffolds for anticancer drug discovery. Based on the literature from 2020 to 2025, this review summarises that structurally diverse imidazoles, particularly ether-linked and long-chain variants, exhibit robust anticancer activity through multi-target protein inhibition and minimal off-target effects. Indoles trigger apoptosis and inhibit angiogenesis, while pyrimidines and their hybrids exhibit nanomolar potency and often outperform conventional chemotherapy. These scaffolds collectively modulate important pathways in cancer and exhibit enhanced selectivity toward tumour cells; however, clinical translation is challenging mainly due to incomplete mechanism of action and pharmacokinetics. Further rational optimisation and green synthesis methods may accelerate the development of these heterocycles into next-generation anticancer agents.