Based on the whole life cycle process of the economic exploitation of natural gas hydrate, this paper proposes the basic problem of stabilizing the wellbore for the basic conditions that must be met to ensure the integrity of the wellbore for exploitation: revealing the complex mechanism of fluid–solid–heat coupling in the process of the physical exchange of equilibrium among gas, water, and multiphase sand flows in the wellbore, hydrate reservoir, and wellbore, defining the interface conditions to ensure wellbore stability during the entire life cycle of hydrate production and proposing a scientific evaluation system of interface parameters for wellbore integrity.