The complex interaction between projected changes in climate and land use across the 60,000 km2 Coweeta LTER study area led us to adopt a nested hierarchical framework to examine provisioning, regulating and preserving ecosystem processes and services. However, the research design gives recognition to how processes and services in southern Appalachia depend contextually on forces associated with the Piedmont Megapolitan Region (236,000 km2) in which it is imbedded. This larger region contains Atlanta and other major southeastern urban centers surrounding southern Appalachia. Sampling, experimental manipulations, and modeling are designed to capture interactions within a range of distinct landscapes reflecting the flowpaths, habitats, and human communities characteristic of southern Appalachia. We work across a range of scales from coarse to fine consisting of (1) regional basins, (2) sub-basins, (3) headwater watersheds, and (4) hillslopes and riparian zones. This flowpath network with intervening natural and built spaces extends upstream from the perennial stream system through transitional, intermittent and ephemeral phases terminating in unchannelized hillslopes. A critical aspect of the research is that study sites are co-located so that different groups of collaborating investigators can obtain complementary measures to produce comprehensive descriptions of local system status and dynamics. Hillslope and riparian zone responses are being characterized at a spatial resolution relevant to the targeted processes using observational and manipulative approaches. Socio-ecological gradients of sub-basins and headwater watersheds are being intensively sampled using instruments, observational, arms-length, and face-to-face procedures. Regional basin patterns and responses are being extensively sampled using direct measurements, remote sensing products, socioeconomic databases, and government sources. We synthesize and upscale observational and experimental research using a process-based approach designed to resolve cross-scale interactions among gradients in moisture, microclimate, settlement intensity, and regulatory environment.