Lycopene is one of the most important carotenoids derived from plant foods, which has been evidenced for its antioxidant effect and inhibition against prostate cancer and cardiovascular diseases. In fresh plant foods, lycopene predominantly exists in the all-trans configuration. However, previous studies revealed that all-trans lycopene presents lower bioactivity and bioavailability than its cis-isomers. Thus, in order to upgrade the nutritional quality of lycopene-rich products, it is of much importance to promote the isomerization of lycopene using various food processing technologies such as light, heating, oxidation, pH, and surfactant, of which heating is the most convenient and economical. In the present article, we review the mechanism of thermal isomerization of lycopene and discuss the factors affecting the thermal isomerization of lycopene in model and actual food systems such as solvent type, heating temperature, and heating time. It is concluded that solvent type and the food matrix can exert great influence on the thermal isomerization of lycopene and that increasing the heating temperature and time can facilitate the isomerization or even degradation of lycopene. Finally, problems existing in this field of research and future research directions are proposed.