A new study published in the journal ofCureusrevealed that the effects of smoking stretch beyond the lungs and heart, and tobacco use may be a major driver of dermatological disorders like psoriasis, atopic dermatitis, premature skin aging, and even skin cancer. The research analyzed data from 350 patients, which highlights the toxic impact of smoking that extends to the skin through mechanisms of oxidative stress and inflammation. Studies report that smoking induces cellular damage that accelerates aging and increases susceptibility to chronic inflammatory skin diseases. The objective of this study was to explore how smoking influences dermatological health by combining clinical, laboratory, and computational analyses. Using retrospective data, this research evaluated demographic and clinical characteristics, inflammatory biomarkers, and smoking exposure levels (measured in pack-years). Advanced statistical tests were employed to assess relationships between smoking status and skin disorders. This study also attempted to build predictive models using modern machine learning tools such as Random Forest, Logistic Regression, XGBoost, and LightGBM. While these algorithms failed to produce reliable predictions (area under the curve < 0.50), they revealed which biological factors most influenced skin disease outcomes. Of the 350 participants, 51.1% were men and 48.9% were women, with an average age of 51.4 years. Nearly half (46.9%) were current smokers. Also, current smokers had a much higher lifetime tobacco exposure when compared to former smokers (t = 2.53, p = 0.013). The findings showed associations between smoking and psoriasis (χ² = 21.38, p < 0.001). There was an increased prevalence of atopic dermatitis among smokers (χ² = 14.27, p < 0.001). Accelerated skin aging was observed more frequently in smokers (χ² = 12.61, p < 0.001) Skin cancer risk was significantly elevated in patients who smoke (χ² = 18.64, p < 0.001). Also, no statistical link was found between smoking and acne severity, treatment response, or other medical comorbidities. Despite the low predictive success of machine learning models, the analysis identified C-reactive protein (CRP), interleukin-6 (IL-6), pack-years, and age as the strongest indicators of skin disease risk among smokers. These findings suggest that systemic inflammation and cumulative tobacco exposure play critical roles in skin pathology. Overall, this study emphasizes that smoking history should be a routine part of dermatological assessments. Integrating smoking cessation counseling into skin care practice could become an essential preventive strategy for both cosmetic and clinical health. Yousaf, J., Sakina, S., Saeed, A., Aftab, M., Khattak, M. I., Elrefae, A., Qandeel, M., & Hameed, A. (2025). Dermatological manifestations of smoking-induced oxidative stress and inflammation: A multifaceted analysis of cutaneous aging and disease progression. Cureus.https://doi.org/10.7759/cureus.94147