Abstract: MXene, as a new class of two-dimensional transition metal carbide/nitride materials, is rapidly emerging. Due to its unique two-dimensional structure and excellent physicochemical properties such as hydrophilicity, antibacterial properties, MXene materials are widely used in constructing high-performance separation membranes and show promising prospects in various separation systems. Unlike previous reviews on MXene-based separation membranes, this article summarizes the research progress on MXene layered composite nanofiltration membranes from the perspective of the types and dimensions of interlayer composite materials, highlighting key issues that need to be addressed to further advance the field. This article first discusses the challenges faced by MXene-based layered composite membranes in nanofiltration and the basic requirements for practical separation applications. By using different type and dimensional nanomaterials for interlayer composites with MXene, the design strategies for MXene layered nanofiltration composite membranes with desired microstructure and multicomponent characteristics are briefly summarized. On this basis, it further introduces the broad application prospects of MXene layered composite membranes in nanofiltration, including seawater desalination and wastewater treatment. Finally, the challenges faced by MXene layered composite nanofiltration membranes are analyzed, and the future research and development directions are outlined.