Advances in synthetic cell biology are enabling the design of cell-like systems with programmable structures and functions, offering new opportunities to investigate and manipulate interactions among microbes, host immunity, and human health. This Special Issue will highlight emerging concepts, enabling technologies, and biomedical applications at the interface of synthetic cells, microbial systems, and immunology. Topics of interest include top-down and bottom-up strategies for synthetic cell construction; minimal and cell-free systems; engineered interactions between synthetic cells and microorganisms; microbial competition, cooperation, and communication; immune recognition and biological compatibility; and synthetic cell-based approaches for modulating host-microbe interactions. The issue will also explore the use of synthetic cells and engineered microbial platforms in microbiome research, precision drug delivery, vaccines, diagnostics, biosensing, and personalized medicine. Particular attention will be given to their potential applications in infectious diseases, cancer, and microbiome-associated disorders. Contributions addressing computational and artificial intelligence-assisted design, translational challenges, biosafety, biosecurity, and ethical considerations are also welcome. By bringing together researchers from synthetic biology, microbiology, immunology, biomaterials, and translational medicine, this Special Issue aims to provide a multidisciplinary forum for advancing next-generation living and cell-inspired technologies.