This guide provides an in-depth analysis of the technical characteristics of the three major substrate materials—FR-4, PTFE, and ceramic—offering a systematic decision-making process that encompasses signal rates, thermal management requirements, and cost control. The article not only covers the performance boundaries of low-loss FR-4 and PTFE, along with the thermal management advantages of ceramic substrates, but also introduces cutting-edge solutions such as hybrid structure designs. It includes detailed selection matrix diagrams and answers to five common questions, providing engineers with a practical reference framework for addressing high-speed digital, high-frequency RF, and high-power application scenarios.