<p>One of the essential cellular machinations co-opted by the WNT signaling pathway, including its canonical β-Catenin and non-canonical WNT/PCP and WNT/ Ca²⁺ sub-pathways, are events such as apoptosis, cancer cell metabolism, inflammation, and proliferation of cancer cells. This review article discusses, in detail, the molecular mechanism of action of the WNT signaling pathway and its components, and digression into evolutionary conservation, but focuses on WNT signaling in development and cancer biology. It also discusses WNT signaling components and the potential role in colorectal cancer (CRC) targeted therapy. The emphasis of the review is on the potential of bioactive compounds, Flavonoids, including Curcumin and Resveratrol, to block WNT signaling and present an opportunity for CRC therapy. It highlights new and existing inhibitors that modulate the WNT pathway, and describes the mechanisms and the evidence for clinical efficacy of these drugs and compounds. This review also provides a comprehensive analysis and talks about ground-breaking discoveries of WNT pathway components and their novel roles in cancer stemness, metastasis, and immune surveillance. As such, this article described the progress toward accumulating evidence of targeting the WNT pathway, describing the clinical trials targeting PORCN inhibitors, FZD antagonists, and inhibitors of β-Catenin transcriptional activity, making it a thorough search of the WNT signaling pathway in cancer that provides potential therapeutic opportunities.</p> Graphical Abstract <p>The diagram explains the WNT signaling pathway, which involves two main pathways: the canonical pathway with β-Catenin, and the non-canonical pathways like WNT/PCP and Wnt/Ca²⁺. These pathways influence various biochemical processes such as apoptosis, cancer metabolism, inflammation, and cancer cell proliferation. Additionally, the diagram highlights compounds like Flavonoids, Curcumin, and Resveratrol that can inactivate WNT signaling, which is relevant in cancer treatment.</p> <p></p>