Microorganisms, as one of the Earth"s most abundant genetic resources, demonstrate tremendous application potential in fields such as medicine, energy, and environmental protection. However, natural microorganisms often suffer from poor stability and low catalytic efficiency. The emergence of microorganism-nanomaterial hybrid systems offers novel strategies to overcome these limitations. These systems integrate nanomaterials with microorganisms or their components (e.g., cell membranes, metabolites, or biomacromolecules) through methods such as biomineralization, electrostatic assembly, surface modification, and genetic engineering. This enables programmable design from the nanoscale to the macroscale, demonstrating broad application prospects and attracting extensive research interest. First, microbial-nanomaterial hybrid systems are classified based on the types of nanomaterials (organic, inorganic, organic-inorganic) and microorganisms (bacteria, fungi, viruses, algae, probiotics). Both types of systems leverage the unique catalytic selectivity of microorganisms and the diverse physicochemical properties of nanomaterials to achieve multidimensional synergy. Their synergistic mechanisms involve both the biochemical processes of microorganisms and the surface/interface reactions of nanomaterials, representing a multidisciplinary achievement spanning microbial interface engineering, biomimetic catalysis, controllable nanomaterial fabrication, and interfacial transport and reaction processes. Next, the application progress in biomedical fields (such as anti-infection, intestinal diseases, and cancer therapy) and energy conversion (e.g., light-driven hybrid systems for proton reduction to hydrogen, CO₂ reduction and conversion, and nitrogen fixation) is elaborated in detail, highlighting their significant advantages in functional integration and synergistic performance. Microorganism–nanomaterial hybrid systems combine the specific recognition and precise metabolic capabilities of microorganisms with the catalytic, drug-delivery, and optoelectronic functions of nanomaterials, enabling the construction of various multifunctional synergistic platforms for catalysis, diagnosis, and therapy. These advances have greatly promoted development in nanomedicine, energy, and environmental applications. In medical contexts, such systems utilize the natural chemotaxis of microorganisms for precise targeting, achieve controlled drug release through environmentally responsive delivery and metabolic regulation, and enhance therapeutic efficacy via combined chemical-biological treatments and immune modulation. Improved biosafety can be achieved through attenuated microbial designs and nanomaterial coatings, offering diverse strategies for the precise treatment of various diseases. In the energy sector, the excellent light-harvesting properties of semiconductor materials and the precise catalytic capabilities of biological systems have been integrated to successfully construct light-driven biocatalytic systems, significantly improving light utilization efficiency. Finally, this review discusses the key challenges facing the practical application of these systems. Nanomaterials may exert toxic effects on microorganisms, impairing their activity and raising environmental safety concerns. The potential release of engineered nanomaterials into ecosystems necessitates careful risk assessment and long-term monitoring. In real-world environments, microbial functions are easily compromised, nanostructures are prone to damage, and reactive oxygen species (ROS) tend to accumulate, resulting in insufficient system stability. Stringent culture conditions, costly raw materials, and significant batch-to-batch variability hinder large-scale production and commercialization. The synergistic mechanisms between microorganisms and nanomaterials are not yet fully understood, particularly regarding molecular-level interactions and long-term compatibility. In medical applications, off-target risks persist due to unpredictable microbial colonization and immune responses, while environmental applications lack sufficient selective recognition capabilities, indicating a need for improved targeting and specificity. Furthermore, interdisciplinary barriers between biology, materials science, and engineering complicate collaborative innovation, and the absence of well-established standards for evaluation, regulation, and scalability also constrains further development. Future efforts should focus on enhancing biocompatibility, optimizing fabrication processes, and establishing comprehensive safety and performance standards to accelerate the transition of these promising systems from laboratory research to real-world applications.