The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, including development, tissue homeostasis, and cell proliferation. Abnormal activation of this pathway due to mutations in key components, epigenetic modifications, and crosstalk with other signaling pathways contributes significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have shown promising prospects in cancer treatment. This review aims to summarize the latest advances in understanding the role of the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing insights into current opportunities and challenges in cancer research and treatment. The Wnt/β-catenin pathway is a highly conserved signaling cascade that involves the binding of Wnt ligands to frizzled receptors (FZD) and LRP5/6 co-receptors, leading to the activation of β-catenin. The pathway is tightly regulated by destruction complexes composed of APC, AXIN, GSK3β, CK1α, and β-TrCP, which control β-catenin levels. Dysregulation of this pathway through mutations in genes like APC, AXIN, and CTNNB1, as well as epigenetic modifications, can lead to cancer development. The review also discusses the role of various regulators, including sFRPs, WIF, GPCs, R-spondins, DKKs, FOXK1, Dab2, PP1, PP2A, RUNX family, Twa, ICAT, Kdm2a/b, and non-coding RNAs, in modulating the Wnt/β-catenin pathway. Additionally, the review explores the cross-talk between the Wnt/β-catenin pathway and other signaling pathways such as TGF-β, Notch, Hippo, Hedgehog, NF-κB, and Ras/Raf/Mek/Erk, highlighting their complex interactions. The up-regulation of the Wnt/β-catenin pathway is implicated in various cancers, including colorectal, gastric, and prostate cancer, and its dysregulation can promote tumor cell proliferation, migration, and resistance to chemotherapy. The review concludes by discussing the potential of targeting the Wnt/β-catenin pathway as a therapeutic strategy in cancer treatment.The Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, including development, tissue homeostasis, and cell proliferation. Abnormal activation of this pathway due to mutations in key components, epigenetic modifications, and crosstalk with other signaling pathways contributes significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have shown promising prospects in cancer treatment. This review aims to summarize the latest advances in understanding the role of the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing insights into current opportunities and challenges in cancer research and treatment. The Wnt/β-catenin pathway is a highly conserved signaling cascade that involves the binding of Wnt ligands to frizzled receptors (FZD) and LRP5/6 co-receptors, leading to the activation of β-catenin. The pathway is tightly regulated by destruction complexes composed of APC, AXIN, GSK3β, CK1α, and β-TrCP, which control β-catenin levels. Dysregulation of this pathway through mutations in genes like APC, AXIN, and CTNNB1, as well as epigenetic modifications, can lead to cancer development. The review also discusses the role of various regulators, including sFRPs, WIF, GPCs, R-spondins, DKKs, FOXK1, Dab2, PP1, PP2A, RUNX family, Twa, ICAT, Kdm2a/b, and non-coding RNAs, in modulating the Wnt/β-catenin pathway. Additionally, the review explores the cross-talk between the Wnt/β-catenin pathway and other signaling pathways such as TGF-β, Notch, Hippo, Hedgehog, NF-κB, and Ras/Raf/Mek/Erk, highlighting their complex interactions. The up-regulation of the Wnt/β-catenin pathway is implicated in various cancers, including colorectal, gastric, and prostate cancer, and its dysregulation can promote tumor cell proliferation, migration, and resistance to chemotherapy. The review concludes by discussing the potential of targeting the Wnt/β-catenin pathway as a therapeutic strategy in cancer treatment.