Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ATP-binding cassette super-family G member 2 (ABCG2), P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, histone deacetylase (HDAC)/Sirtuin-1, proteasome, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) kinase, matrix metalloproteinases (MMP)-2/9, Janus kinases (JAK)/Signal transducer and activator of transcription proteins (STAT) signaling pathways, Cell Division Cycle-25 (CDC25B), tubulin, cathepsin-K, topoisomerase-II, Wingless-related integration site (Wnt), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), v-raf murine sarcoma viral oncogene homolog B1 (B-Raf), mammalian target of rapamycin (mTOR), etc.