and are important in various technological fields such as energy, electronics, medicine, and many more. [1][2][3][4][5] However, as a consequence of industrial processes and man-made pollution, unwanted nanoparticle size distributions and concentrations [6] give rise to concerns with respect to human health and environmental pollution. While the nanoparticles' physicochemical properties (size, shape, surface chemistry, etc.) determine the quality of products, [7,8] such characteristics are also important in order to evaluate the biological impact of nanoparticles at a molecular, cellular, and systemic level for any risk assessment for environmental and human health. [9] Characterizing nanoparticles in a dynamic context and on a case-by-case basis, microscopic imaging techniques including those that use focused electron or ion beams in scanning electron microscopes (SEMs) or helium ion microscopes [10] (HIMs) to generate nanometer scale spatial resolution are frequently applied in the scientific community. Given the substantial information content of digital images, these techniques often benefit from, or require, automated high-throughput data analysis that enables the accurate identification of large numbers of particles in a robust way.Nanoparticles occur in various environments as a consequence of man-made processes, which raises concerns about their impact on the environment and human health. To allow for proper risk assessment, a precise and statistically relevant analysis of particle characteristics (such as size, shape, and composition) is required that would greatly benefit from automated image analysis procedures. While deep learning shows impressive results in object detection tasks, its applicability is limited by the amount of representative, experimentally collected and manually annotated training data. Here, an elegant, flexible, and versatile method to bypass this costly and tedious data acquisition process is presented. It shows that using a rendering software allows to generate realistic, synthetic training data to train a state-of-the art deep neural network. Using this approach, a segmentation accuracy can be derived that is comparable to man-made annotations for toxicologically relevant metal-oxide nanoparticle ensembles which were chosen as examples. The presented study paves the way toward the use of deep learning for automated, highthroughput particle detection in a variety of imaging techniques such as in microscopies and spectroscopies, for a wide range of applications, including the detection of micro-and nanoplastic particles in water and tissue samples.