High-integrated package of microsystem is based on multi-materials and substrates including die, TSV interposer, HTCC envelope etc. The design of PDN for low-voltage and high-current power supply and interconnect for high-speed signal becomes difficult, due to extremely limited space, mismatch of multi-scale structures and coupling of electromagnetic effects. Taking full account of the approaching scales of microsystem package and chip, and aiming at the application of microsystem in larger system, this paper focus on the CPS co-design and co-simulation method. For the PDN design of the core power, the CPM has been used to simulate the power ripple. Decoupling capacitor networks on TSV substrate, HTCC substrate and PCB have been assigned and co-optimized to realize the stable and clean power supply. For the interconnect design of high-speed signal, coupled field-circuit method has been used to model the package interconnect and analyze the time domain waveform. The configuration of chip electrical characteristics and design of signal interconnect have been balanced to gain the signal integrity. CPS co-design method can effectively utilize the limited space to improve the performance of microsystem.