The rapid evolution of semiconductor technology and the growing demand for heterogeneous integration have positioned advanced packaging as a critical enabler of next-generation electronic systems. As devices become more compact and functionally dense, traditional single-die analysis methods are no longer sufficient. Instead, a system-level approach—spanning from silicon to full system integration—is essential to ensure performance, and reliability. This talk explores how advanced packaging technologies such as 2.5D/3D IC, and chiplets serve as the foundation for silicon-to-system multiphysics analysis. We delve into the multi-scale, multi-domain simulation challenges—including thermal, mechanical, electrical and optical interactions—and examine how state-of-the-art simulation tools and methodologies are bridging the gap between design abstraction levels. Finally, an AI-driven thermal analysis that illustrates how complex chiplet designs influence floorplanning decisions. That proposed approach accelerates design space exploration, enhances prediction accuracy, and enables optimization of packaging architectures—from chiplet interconnects to full-system integration.