Lung cancer (LC) remains the foremost cause of cancer-related mortality across the globe. Non-small cell lung cancer (NSCLC) is a type of LC that exhibits significant heterogeneity at histological and molecular levels. Genetic alterations in upstream signaling molecules activate cascades affecting apoptosis, proliferation, and differentiation. Disruption of these signaling pathways leads to the proliferation of cancer-promoting cells, progression of cancer, and resistance to its treatment. Recent insights into the function of signaling pathways and their fundamental mechanisms in the onset of various diseases could pave the way for new therapeutic approaches. Recently, numerous drug molecules have been created that target these cell signaling pathways and could be used alongside other standard therapies to achieve synergistic effects in mitigating the pathophysiology of NSCLC. Additionally, many researchers have identified several predictive biomarkers, and alterations in transcription factors and related pathways are employed to create new therapeutic strategies for NSCLC. Findings suggest using specific inhibitors to target cellular signaling pathways in tumor progression to treat NSCLC. This review investigates the role of signaling pathways in NSCLC development and explores novel therapeutic strategies to enhance clinical treatment options for NSCLC.