The management of respiratory comorbidities is one of the core challenges in modern medicine. This article aims to go beyond the diagnosis and treatment model of a single disease and propose a comprehensive management framework from common mechanisms to integrated clinical practice. The core of this framework lies in recognizing that there are shared pathophysiological pathways such as chronic inflammation, oxidative stress, immune dysregulation and tissue remodeling behind various respiratory comorbidities. These common mechanisms not only explain the high prevalence of comorbidities but also provide critical targets for cross-disease interventions. At the clinical practice level, successful comorbidity management relies on four pillar strategies: ① early identification and risk assessment, involving proactive screening for comorbidities;② mechanism-guided precision therapy, selecting treatments that target shared pathways to simultaneously address multiple conditions; ③ benefit-risk balanced decision-making, carefully weighing the advantages and disadvantages of different treatment options in the context of multimorbidity, prioritizing strategies that offer the greatest comprehensive net benefit; ④ patient-centered multidisciplinary collaboration, integrating expertise from various specialties to develop individualized holistic management plans. In summary, the future development of respiratory medicine requires a shift from fragmented disease management to an integrated and precise comorbidity management model. Basic mechanism research should combine with individualized clinical decision making. The multidisciplinary teams will play full role. Only in this way, the prognosis and quality of life of patients with complex comorbidities can be effectively optimized.