In this work, the influence of four-wave mixing (FWM) effects on the transverse mode instability (TMI) is incorporated into the TMI model based on stimulated thermal Rayleigh scattering. The model is capable of analyzing the gain characteristics of different high-power fiber amplifiers, based on which the physical mechanism and functioning boundary of FWM are theoretically investigated. Consequently, a new TMI threshold formula is defined to resolve the inconsistencies in the previous TMI models. It is revealed that it is extremely necessary to consider the influence of FWM on TMI in ultra-large mode field laser systems.