Dielectric polymer materials with excellent heat resistance, ultralow dielectric constant, and low dielectric loss are widely used in microelectronics and the aerospace industry. Nonetheless, researching these polymers presents a significant challenge as it requires a precise balancing of various performance aspects of the material. In this study, we propose a materials genome approach to designing and screening thermosetting benzoxazole resins that feature excellent dielectric properties and good heat resistance. Candidate structures are initially designed through high-throughput methods based on the materials genome approach and are subsequently screened in two distinct steps. The most promising resin, 2F-QNBO, is first identified theoretically and subsequently verified experimentally. The results indicate that the cured product of 2F-QNBO exhibits a 5% weight loss temperature (T d5 ) of 547 °C. It shows near-constant dielectric constants from 1 to 10 GHz, stabilizing at 1.96 at 10 GHz and demonstrates a slight increase in dielectric loss over this frequency range, reaching 0.0177 at 10 GHz. Overall, it shows good frequency stability over a wide frequency range. It can also be dissolved in common solvents such as tetrahydrofuran and dichloromethane and features good dielectric properties, excellent molding processability, and high-temperature resistance. This study demonstrates the reliability and effectiveness of a high-throughput design and computational screening method grounded in the concept of materials genomics. It presents an approach for developing dielectric polymers with high thermal stability.