The scarcity of freshwater resources is a major global challenge causedby population and economic growth. Water desalination using a reverse osmosis (RO) membrane is a promising technology to supply potable water from seawater and brackish water. The advancement of RO desalination highly depends on new membrane materials. Currently, the RO technology mainly relies on polyamide thin-film composite (TFC) membranes, which suffer from several drawbacks (e.g., low water permeability, permeability-selectivity tradeoff, and low fouling resistance) that hamper their real-world applications. Nanoscale fillers with specific characteristics can be used to improve the properties of TFC membranes. Embedding nanofillers into TFC membranes using interfacial polymerization allows the creation of thin-film nanocomposite (TFNC) membranes, and has become an emerging strategy in the fabrication of high-performance membranes for advanced RO water desalination. To achieve optimal design, it is indispensable to search for reliable methods that can provide fast and accurate predictions of the structural and transport properties of the TFNC membranes. However, molecular understanding of permeability-selectivity characteristics of nanofillers remains limited, partially due to the challenges in experimentally exploring microscopic behaviors of water and salt ions in confinement. Molecular modeling and simulations can fill this gap by generating molecular-level insights into the effects of nanofillers' characteristics (e.g., shape, size, surface chemistry, and density) on water permeability and ion selectivity. In this review, we summarize molecular simulations of a diverse range of nanofillers including nanotubes (carbon nanotubes, boron nitride nanotubes, and aquaporin-mimicking nanochannels) and nanosheets (graphene, graphene oxide, boron nitride sheets, molybdenum disulfide, metal and covalent organic frameworks) for water desalination applications. These simulations reveal that water permeability and salt rejection, as the major factors determining the desalination performance of TFNC membranes, significantly depend on the size, topology, density, and chemical modifications of the nanofillers. Identifying their influences and the physicochemical processes behind, via molecular modeling, is expected to yield important insights for the fabrication and optimization of the next generation high-performance TFNC membranes for RO water desalination.