Abstract. Potential challenges with managing mechanical stress and the consequent effects on device performance for advanced three-dimensional (3-D) IC technologies are outlined. The growing need in a simulation-based design verification flow capable of analyzing a design of 3-D IC stacks and detecting acrossdie out-of-spec variations in MOSFET electrical characteristics caused by the die thinning and stacking-induced mechanical stress is addressed. The development of a multiscale simulation methodology for managing mechanical stresses during a sequence of designs of 3-D IC dies, stacks, and packages is focused. A set of physics-based compact models for a multiscale simulation is proposed to assess the mechanical stress across the device layers in silicon chips stacked and packaged with the 2.5D interposer-based, and true 3-D through silicon via-based technology. A simulation flow is developed for the hot-spot checking in different types of devices/circuits such as digital, analog, analog matching, memory, IO, characterized by different sensitivities to the stress-induced mobility variations. A calibration technique based on fitting to measured electrical characteristics of the test-chip devices is presented. The limited characterization or measurement capabilities for 3-D IC stacks and a strict "good die" requirement make this type of analysis critical in order to achieve an acceptable level of functional and parametric yield. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.