Abstract: Current diagnostic technologies for bloodstream infections face a dual challenge: the gold standard blood culture is characterized by low positivity rates and time-consuming, while emerging culture-independent techniques show insufficient sensitivity. Improving sensitivity critically depends on efficient isolation and enrichment of pathogens and removing interference from the blood matrix. However, the clinical use of prevailing technologies, such as, centrifugation, microfluidics, dielectrophoresis, field-flow fractionation, acoustophoresis, affinity labeling, are challenged by the high bacterial load dependency, limited sample throughput, and specialized instruments. Consequently, optimizing the isolation and enrichment efficiency systematically, improving device throughput, and reducing costs are essential for the establishment of a rapid detection system for bloodstream pathogens that is both highly sensitive and applicable in clinical practice.