This paper presents an integrated techno-economic framework for the optimal design and operation of a shale gas supply chain network. A 3D coupled compositional reservoir model is constructed utilizing CMG's software suites to simulate realistic drilling, completion, stimulation (DCS) and well-pad production processes, for a specified supply chain network. Several well pad design configurations and operations are selected for shale well development, and re-stimulation and/or stimulation operations are compared for implementation in different well pad designs. Reservoir simulation output data are incorporated into a mixed integer linear programming (MILP) model developed in GAMS optimization software. The Strategic MILP model recommends an optimal drilling strategy, schedule for product transportation, and supply chain network configuration that optimizes after-tax profit. Additionally, the management of freshwater and the recycle of wastewater is developed incorporating the spatial variation of total dissolved solids (TDS) composition from multi-well shale pads. The results show the significant influence of reservoir heterogeneity and implemented DCS strategies, on the profitability of the case study shale gas assets.