Recently, two-dimensional (2D) layered nanomaterials have become promising candidates for surface-enhanced Raman scattering (SERS) substrates due to their unique characteristics of ultrathin layer structure, outstanding optical properties and good biocompatibility, significantly contributing to remarkable SERS sensitivity, stability, and compatibility. Unlike traditional SERS substrates, 2D nanomaterials possess unparalleled layer-dependent, phase transition induced and anisotropic optical properties, which as driving forces significantly promote the SERS performance and development, as well as greatly enrich the SERS substrates and provide versatile resources for SERS research. For a profound understanding of the SERS effect of 2D nanomaterials, a review concentrating on these driving forces for SERS enhancement on 2D nanomaterials is written here for the first time, which strongly emphasizes the importance and influence of these driving forces on the SERS effect of 2D nanomaterials, including their intrinsic physical and chemical properties and external influencing factors. Moreover, the essential mechanisms of these driving forces for the SERS effect are also elaborated systematically. Finally, the challenges and future perspectives of SERS substrates based on 2D nanomaterials are concluded. This review will provide guiding principles and strategies for designing highly sensitive 2D nanomaterial SERS substrates and extending their potential applications based on SERS.