Abstract: Current diagnostic technologies for bloodstream infections face a dual challenge: the gold standard blood culture demonstrates low positivity rates and long turnaround time, while emerging culture-independent techniques show insufficient sensitivity. Enhancing sensitivity critically depends on efficiently separating and enriching pathogens, and removing interference from the blood matrix. However, prevailing technologies (e.g., centrifugation, microfluidics, dielectrophoresis, field-flow fractionation, acoustophoresis, affinity labeling) confront three major clinical implementation barriers: high bacterial load dependency, limited sample throughput, and specialized instruments. Consequently, systematically optimizing separation and enrichment efficiency, enhancing device throughput, and reducing costs are essential for establishing a rapid detection system for bloodstream pathogens that is both highly sensitive and clinically viable.