<p>Most instances of lung cancer (LC), which is the primary cause of cancer-related death worldwide, are non-small-cell lung cancer (NSCLC). Genetic predispositions, environmental exposures, and smoking are risk factors that lead to the development of LC, and the ineffectiveness of existing treatments emphasizes the need for innovative approaches to therapy. Through its regulation of cell proliferation, apoptosis, epithelial-to-mesenchymal transition (EMT), and cancer stem cell maintenance, the Wnt/β-catenin signaling system is essential to advancing LC. This study offers a thorough examination of Wnt/β-catenin signaling in LC, emphasizing how miRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), protein-coding genes, enzymes, and both natural and synthetic drugs affect this signaling. Recent research supports the dual function of Wnt/β-catenin signaling in tumor development and repression, which we describe. We also emphasize the therapeutic potential of Wnt/β-catenin inhibitors despite issues including off-target effects and bioavailability. This study highlights the potential of focusing on Wnt/β-catenin signaling to enhance LC patient outcomes by combining computational studies with molecular insights. It also lays the groundwork for further research and treatment development.</p> Graphical abstract <p></p>