In this chapter we consider the issues related to integrating microarchitectural IP blocks into complex SoCs while satisfying performance, power, thermal, and reliability constraints. We first review different abstraction levels for SoC design that promote IP reuse, and which enable fast simulation for early functional validation of the SoC platform. Since SoCs must satisfy a multitude of interrelated constraints, we then present high-level power, thermal, and reliability models for predicting these constraints. These constraints are not unrelated and their interactions must be considered, modeled and evaluated. Once constraints are modeled, we must explore the design space trading off performance, power and reliability. Several case studies are presented illustrating how the design space can be explored across layers, and what modifications could be applied at design time and/or runtime to deal with reliability issues that may arise.