As van der Waals layered materials are reduced from bulk crystals to monolayer sheets, a host of electronic, optoelectronic, and mechanical properties emerge which differ from those of the parent materials. This variety of materials properties—coupled to the atomically thin form factor—has attracted interest from all research sectors in the past decade due to potential applications in flexible, transparent, and low-power electronics. The two-dimensional nature of these materials makes them extremely sensitive to any surface interactions presenting both a unique opportunity to tune materials properties through surface modification and also a challenge whereby any surface contaminants can dramatically degrade the material quality. In this dissertation, we investigate and utilize this surface sensitivity in three different material systems. First, we investigate electronic transport in germanane, a germanium analog of graphane, through a combination of electronic measurements on multi-layer crystals and finite-element modeling. In addition to doping this 2D material, we uncover a sensitivity of this transport to the presence of water-vapor, as well as an anisotropy between inter- and intra-layer resistivity of up to eleven orders of magnitude. The strong water sensitivity and weak inter-layer coupling mean that the transport in these samples is dominated by the topmost layer and suggests that it may be possible to measure the effects of 2D materials in bulk materials by making electrical contact to only the topmost layer. Second, we report on a templated MoS2 growth technique wherein Mo is deposited onto atomically-stepped sapphire substrates through a SiN stencil with feature sizes down to 100 nm and subsequently sulfurized at high temperature. These films have a quality comparable to the best MoS2 prepared by other methodologies, and the thickness of the resulting MoS2 patterns can be tuned layer by layer by controlling the initial Mo deposition. This approach critically enables the creation of patterned single-layer MoS2 films with pristine surfaces suitable for subsequent modification via functionalization and mechanical stacking. Further, we anticipate that this growth technique should be broadly applicable within the family of transition metal dichalcogenides. Third and finally, we present progress toward understanding how local changes to graphene’s crystal structure, such as defects, adatoms, and electromagnetic fields, affect the observable electronic and spin transport. We developed experimental methods to perform scanning probe and scanning tunneling microscopy with the simultaneous measurement of electrical transport in graphene Hall bar devices synthesized from graphene grown by chemical vapor deposition. Through the combination of these powerful experimental techniques, we plan to investigate the connection between localized surface modifications of graphene and the electronic and spin transport in these devices with eventual expansion of this technique to other 2D materials.