Simple SummaryThe treatment of lung cancer poses a challenge due to the alterations in the characteristics of the same cancer cell. The altered characteristics make therapeutic strategies dynamic and evolutionary. To create a more appropriate therapeutic strategy for patients with lung cancer and improve their prognosis, we need to know how the alterations occur and how the alterations affect the treatment. This review aims to summarize the various variations in cancer characteristics and describe a more comprehensive multidisciplinary therapeutic strategy for lung cancer.AbstractThe diagnosis and treatment of lung cancer (LC) is always a challenge. The difficulty in the decision of therapeutic schedule and diagnosis is directly related to intratumoral heterogeneity (ITH) in the progression of LC. It has been proven that most tumors emerge and evolve under the pressure of their living microenvironment, which involves genetic, immunological, metabolic, and therapeutic components. While most research on ITH revealed multiple mechanisms and characteristic, a systemic exposition of ITH in LC is still hard to find. In this review, we describe how ITH in LC develops from the perspective of space and time. We discuss elaborate details and affection of every aspect of ITH in LC and the relationship between them. Based on ITH in LC, we describe a more accurate multidisciplinary therapeutic strategy on LC and provide the newest opinion on the potential approach of LC therapy.