The extensive depletion of the development target triggers the demand for infill drilling in the upside target of multilayer unconventional reservoirs. However, such an infill scheme in the field practice still heavily relies on empirical knowledge or pressure responses, and the geomechanics consequences have not been fully understood. Backed by the data set from the Permian Basin, in this work we present a novel integrated reservoir-geomechanics-fracture model to simulate the spatiotemporal stress evolution and locate the optimal development strategy in the upside target of the Bone Spring Formation. An embedded discrete fracture model (EDFM) is deployed in our fluid-flow simulation to characterize complex fractures, and the stress-dependent matrix permeability and fracture conductivity are included through the compaction/dilation option. After calibrating reservoir and fracture properties by history matching of an actual well in the development target (i.e., third Bone Spring), we run the finite element method (FEM)-based geomechanics simulation to model the 3D stress state evolution. Then a displacement discontinuity method (DDM) hydraulic fracture model is applied to simulate the multicluster fracture propagation under an updated heterogeneous stress field in the upside target (i.e., second Bone Spring). Numerical results indicate that stress field redistribution associated with parent-well production indeed vertically propagates to the upside target. The extent of stress reorientation at the infill location mainly depends on the parent-child horizontal offset, whereas the stress depletion is under the combined impact of horizontal offset, vertical offset, and infill time. A smaller parent-child horizontal offset aggravates the overlap of the stimulated reservoir volume (SRV), resulting in more substantial interwell interference and less desirable oil and gas production. The same trend is observed by varying the parent-child vertical offset. Moreover, the efficacy of an infill operation at an earlier time is less affected by parent-well depletion because of the less-disturbed stress state. The candidate infill-well locations at various infill timings are suggested based on the parent-well and child-well production cosimulation. Being able to incorporate both pressure and stress responses, the reservoir-geomechanics-fracture model delivers a more comprehensive understanding and a more integral solution of infill-well design in multilayer unconventional reservoirs. The conclusions provide practical guidelines for the subsequent development in the Permian Basin.