Dielectric substrates with low dielectric constant and good thermal stability are highly desired for high-frequency and high-speed signal transmission. It is however challenging to rationally design the demand-satisfied polymer-based composites due to the inadequate understanding of the contradictory effect of inorganic fillers on modulating dielectric-thermal-mechanical properties. In this work, taking Polytetrafluoroethylene (PTFE)-SiO2 composite as the example, we perform high-throughput finite-element calculations to systematically study the filler effects on the dielectric constant of composites εrcomposite and the coefficient of thermal expansion of composites (CTE-c). A series of influencing factors including intrinsic property, volume fraction, shape, distribution, and orientation of fillers have been considered in our models to establish the structure-property mapping of dielectric composites. It is found that CTE-c is more sensitive to the filler structure of PTFE-SiO2 composites than εrcomposite. Finally, guided by the calculation results, a skeleton structure is proposed to realize the performance targets of εrcomposite< 2.3 and CTE-c < 60 ppm/K with lower SiO2 filler content. This work provides a universal data-driven strategy for the rational design of dielectric composites with multi-objective requirements, and it is expected to spark more experimental efforts to design novel dielectric composites for high-quality signal transmission.