The Wnt/β-catenin signaling pathway plays a crucial role in cancer development and therapy response by facilitating cancer stem cell renewal, cell proliferation, and differentiation. Accumulated research highlights the therapeutic potential of agents targeting this pathway in various cancers. Key components of the Wnt/β-catenin cascade, including the Wnt ligand/receptor interface, β-catenin destruction complex, and TCF/β-catenin transcription complex, have been targeted in preclinical and clinical evaluations. This review outlines the latest progress and perspectives on Wnt/β-catenin signaling pathway targeted therapy in different cancer types. Understanding the inhibitors, antagonists, and activators of this pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are needed to confirm precise and secure targeted agents and achieve optimal clinical benefits in malignant diseases.The Wnt/β-catenin signaling pathway plays a crucial role in cancer development and therapy response by facilitating cancer stem cell renewal, cell proliferation, and differentiation. Accumulated research highlights the therapeutic potential of agents targeting this pathway in various cancers. Key components of the Wnt/β-catenin cascade, including the Wnt ligand/receptor interface, β-catenin destruction complex, and TCF/β-catenin transcription complex, have been targeted in preclinical and clinical evaluations. This review outlines the latest progress and perspectives on Wnt/β-catenin signaling pathway targeted therapy in different cancer types. Understanding the inhibitors, antagonists, and activators of this pathway rationalizes innovative strategies for personalized cancer treatment. Further investigations are needed to confirm precise and secure targeted agents and achieve optimal clinical benefits in malignant diseases.