Synthetic genomics (SynGen) has emerged as a new game-changing platform for future crop improvement by allowing the design and construction of designer-made plant genomes for sustainable agriculture. This chapter first discussed the conceptual and technological foundations of SynGen for future genome design. We investigated how SynGen is being applied to improve yield, stress tolerance, nutritional profile, metabolic pathway engineering, plant–microbe interactions, and to design minimal or fully synthetic plant genomes. Integration with multi-omics, biofoundries, and gene drives further expands its capability to fast-track future crop design. Nevertheless, widespread application encounters major technical, ethical, and regulatory challenges, along with some bottlenecks and implications of redesigned crops, which demand transparent governance and inclusive public dialogue. To address these issues, we propose that innovations in synthetic biology and public–private collaborations could assist in the design of future climate-smart, high-performance crops. In short, SynGen could serve as a game-changing approach that can help achieve global food security in the face of changing climate.