The 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.