The intrinsically anisotropic crystallinity of two-dimensional (2D) transition metal dichalcogenide (2D TMD) layers enables a variety of intriguing material properties which strongly depend on the physical orientation of constituent 2D layers. For instance, 2D TMDs with vertically-aligned layers exhibit numerous dangling bonds on their 2D layer edge sites predominantly exposed on the surface, projecting significantly improved physical and/or chemical adsorption capability compared to their horizontally-oriented 2D layer counterparts. Such property advantages can be further promoted as far as the material can be integrated onto unconventional substrates of tailored geometry/functionality, offering vast opportunities for a wide range of applications which demand enhanced surface area/reactivity and mechanical flexibility. Herein, we report a new form of 2D TMDs, i.e., three-dimensionally ordered 2D molybdenum disulfide (2D MoS2) with vertically-aligned layers integrated on elastomeric substrates and explore their tunable multi-functionalities and technological promise. We grew large-scale (>2 cm2) vertically-aligned 2D MoS2 layers using a three-dimensionally patterned silicon dioxide (SiO2) template and directly transferred/integrated them onto flexible polydimethylsiloxane (PDMS) substrates by taking advantage of the distinguishable water-wettability of 2D MoS2vs. SiO2. The excellent structural integrity of the integrated vertical 2D MoS2 layers was confirmed by extensive spectroscopy/microscopy characterization. In addition, the stretch-driven unique tunability of their optical and surface properties was also examined. Moreover, we applied this material for flexible humidity sensing and identified significantly improved (>10 times) sensitivity over conventionally-designed horizontal 2D MoS2 layers, further confirming their high potential for unconventional flexible technologies.