ConspectusTwo-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), in particular molybdenum disulfide (MoS2), have recently attracted huge interest due to their proper bandgap, high mobility at 2D limit, and easy-to-integrate planar structure, which are very promising for extending Moore's law in postsilicon electronics technology. Great effort has been devoted toward such a goal since the demonstration of protype MoS2 devices with high room-temperature on/off current ratios, ultralow standby power consumption, and atomic level scaling capacity down to sub-1-nm technology node. However, there are still several key challenges that need to be addressed prior to the real application of MoS2-based electronics technology. The controllable growth of wafer-scale single-crystal MoS2 on industry-compatible insulating substrates is the prerequisite of application while the currently synthesized MoS2 films mostly are polycrystalline with limited sizes of single-crystal domains and may involve metal substrates. The precise layer-control is also very important for MoS2 growth since its electronic properties are layer-dependent, whereas the layer-by-layer growth of multilayer MoS2 dominated by the van der Waals (vdW) epitaxy leads to poor thickness uniformity and noncontinuously distributed domains. High density up to 1013 cm-2 of sulfur vacancies (SVs) in grown MoS2 can cause unfavorable carrier scatting and electronic properties variations and will inevitably disturb the device performance. The dangling-bond-free surface of MoS2 gives rise to an inherent vdW gap at metal-semiconductor (M-S) contact, which leads to high electrical resistance and poor current-delivery capability at the contact interface and thereby substantially limits the performances of MoS2 devices.In this Account, we briefly review recent experimental and theoretical attempts for addressing the aforementioned challenges and present our own insights from atomistic simulations. We theoretically revealed the vital role of substrate steps for guiding unidirectional nucleation of monolayer MoS2 and uniform nucleation and edge-aligned growth of bilayer MoS2 by advanced simulations. The established thermodynamic mechanisms have successfully directed the experimental works on the controllable growth of 2 in. single-crystal monolayer and centimeter-scale uniform bilayer MoS2. The postgrowth repair mechanism of SV defect in MoS2 via thiol chemistry treatment has been theoretically explored with the consideration of side reaction of surface functionalization to help experimentally reduce SV defect density by 75%. Beyond the atomic level understanding, theoretical simulations proposed the electronic states hybridization mechanism across the semimetal-MoS2 vdW interface, thereby guiding experimental effort for realizing Ohmic contact at the MoS2-Sb(0112) vdW interface with record-low contact resistance.These advances provide a sound basis with an atomic-level understanding for addressing the related issues. However, there are still notable gaps in terms of system size and time scale of dynamics between atomistic simulations and experimental observations for the studies of MoS2 growth and interfaces. The combination of multiscale simulations and artificial intelligence technology is expected to narrow these gaps and provide a more insightful understanding of the controllable growth and interfacial properties modulation of MoS2. We conclude the Account with the standing challenges and outlook on future research directions from the theoretical perspective.