The WNT-β-catenin signaling pathway plays a crucial role in various developmental processes and adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability, and apoptosis. Aberrant regulation of this pathway is associated with numerous diseases, including cancer, fibrosis, and neurodegeneration. Despite its importance, therapeutic agents targeting the WNT pathway have only recently entered clinical trials, and none have been approved yet. The complexity of the WNT signaling cascade, which involves multiple ligands, receptors, and co-receptors, poses significant challenges in developing safe and effective therapeutics. Additionally, the pathway's dual roles in both canonical and non-canonical signaling further complicate its targeting. Recent efforts to modulate the WNT signaling cascade have shown promise, but the precise balance between activating and inhibiting WNT signaling remains a critical issue. The review discusses the challenges and potential solutions in developing therapeutic strategies for the WNT pathway, emphasizing the need for personalized approaches to address the diverse effects of WNT signaling in different diseases.The WNT-β-catenin signaling pathway plays a crucial role in various developmental processes and adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability, and apoptosis. Aberrant regulation of this pathway is associated with numerous diseases, including cancer, fibrosis, and neurodegeneration. Despite its importance, therapeutic agents targeting the WNT pathway have only recently entered clinical trials, and none have been approved yet. The complexity of the WNT signaling cascade, which involves multiple ligands, receptors, and co-receptors, poses significant challenges in developing safe and effective therapeutics. Additionally, the pathway's dual roles in both canonical and non-canonical signaling further complicate its targeting. Recent efforts to modulate the WNT signaling cascade have shown promise, but the precise balance between activating and inhibiting WNT signaling remains a critical issue. The review discusses the challenges and potential solutions in developing therapeutic strategies for the WNT pathway, emphasizing the need for personalized approaches to address the diverse effects of WNT signaling in different diseases.