The Wnt/β-catenin signaling pathway is crucial in physiological processes like development, tissue homeostasis, and cell proliferation. Abnormal activation of this pathway, due to mutations, epigenetic changes, or interactions with other pathways, contributes to tumor initiation and progression. Therapies targeting this pathway show promise for cancer treatment, with many drugs in development. This review summarizes the latest understanding of the Wnt/β-catenin pathway's role in carcinogenesis and targeted therapy, highlighting current opportunities and challenges in cancer research and treatment. The Wnt/β-catenin pathway consists of four segments: extracellular, membrane, cytoplasmic, and nuclear. Wnt proteins, secreted by the body, initiate the pathway by binding to FZD and LRP5/6 receptors. The pathway involves key components like β-catenin, DVL, GSK3β, AXIN, APC, and CK1. Upon Wnt binding, β-catenin is stabilized and transported to the nucleus, where it activates Wnt target genes by interacting with TCF/LEF and co-activators. The Wnt/β-catenin pathway plays a critical role in determining cell fate, promoting cell proliferation, and regulating embryonic development, stem cell maintenance, and self-renewal. Dysregulation of this pathway is frequently associated with various diseases, including cancer. Activation of the pathway leads to the expression of target genes like cyclin D1, c-Myc, and Axin2, which regulate cell proliferation, migration, and stem cell properties. The pathway is also involved in maintaining the self-renewal ability of cancer stem cells (CSCs), which contribute to tumor development, drug resistance, and metastasis. Regulators targeting the Wnt/β-catenin pathway include sFRPs, WIF, glypicans, Tiki, and Notum, which modulate the pathway through various mechanisms. Regulators targeting FZD and LRP5/6 include R-spondins, Norrin, and DKK, which influence the pathway by activating or inhibiting it. Regulators targeting DVL include FOXK1, FOXK2, and Dab2, which interact with DVL to promote or inhibit the pathway. Regulators targeting the destruction complex (DC) include Dab-2, PP1, PP2A, and Twa, which influence the degradation of β-catenin. Regulators targeting β-catenin include ICAT, Kdm2a/b, and other proteins that modulate β-catenin methylation and demethylation, thereby regulating the pathway. Epigenetic modifications, such as DNA methylation and histone modifications, also play a role in regulating the Wnt/β-catenin pathway. Noncoding RNAs, including miRNAs and lncRNAs, regulate the pathway by targeting key components like β-catenThe Wnt/β-catenin signaling pathway is crucial in physiological processes like development, tissue homeostasis, and cell proliferation. Abnormal activation of this pathway, due to mutations, epigenetic changes, or interactions with other pathways, contributes to tumor initiation and progression. Therapies targeting this pathway show promise for cancer treatment, with many drugs in development. This review summarizes the latest understanding of the Wnt/β-catenin pathway's role in carcinogenesis and targeted therapy, highlighting current opportunities and challenges in cancer research and treatment. The Wnt/β-catenin pathway consists of four segments: extracellular, membrane, cytoplasmic, and nuclear. Wnt proteins, secreted by the body, initiate the pathway by binding to FZD and LRP5/6 receptors. The pathway involves key components like β-catenin, DVL, GSK3β, AXIN, APC, and CK1. Upon Wnt binding, β-catenin is stabilized and transported to the nucleus, where it activates Wnt target genes by interacting with TCF/LEF and co-activators. The Wnt/β-catenin pathway plays a critical role in determining cell fate, promoting cell proliferation, and regulating embryonic development, stem cell maintenance, and self-renewal. Dysregulation of this pathway is frequently associated with various diseases, including cancer. Activation of the pathway leads to the expression of target genes like cyclin D1, c-Myc, and Axin2, which regulate cell proliferation, migration, and stem cell properties. The pathway is also involved in maintaining the self-renewal ability of cancer stem cells (CSCs), which contribute to tumor development, drug resistance, and metastasis. Regulators targeting the Wnt/β-catenin pathway include sFRPs, WIF, glypicans, Tiki, and Notum, which modulate the pathway through various mechanisms. Regulators targeting FZD and LRP5/6 include R-spondins, Norrin, and DKK, which influence the pathway by activating or inhibiting it. Regulators targeting DVL include FOXK1, FOXK2, and Dab2, which interact with DVL to promote or inhibit the pathway. Regulators targeting the destruction complex (DC) include Dab-2, PP1, PP2A, and Twa, which influence the degradation of β-catenin. Regulators targeting β-catenin include ICAT, Kdm2a/b, and other proteins that modulate β-catenin methylation and demethylation, thereby regulating the pathway. Epigenetic modifications, such as DNA methylation and histone modifications, also play a role in regulating the Wnt/β-catenin pathway. Noncoding RNAs, including miRNAs and lncRNAs, regulate the pathway by targeting key components like β-caten