Background: Delays in diagnosing and treating sepsis increase mortality. Hospitals increasingly combine nursing-led screening with laboratory rapid diagnostics to accelerate recognition and antimicrobial therapy. We aimed to systematically review the effects of integrated nursing-led sepsis screening and laboratory rapid diagnostics on time-to-antibiotics, antibiotic utilization, and mortality among hospitalized adults. Method: Data sources include MEDLINE, Embase, CINAHL, and CENTRAL were searched from inception to 19 October 2025. We include original studies evaluating nursing-led screening or protocols and/or laboratory rapid diagnostics (rapid blood-culture ID or rapid phenotypic AST), reporting at least one outcome of interest. Two reviewers screened, extracted data, and assessed risk of bias (quasi-experimental studies by ROBINS-I; RCTs by RoB 2). Heterogeneity precluded meta-analysis; results were narratively synthesized. Results: Eleven studies (4 emergency department nurse-driven protocols; 3 hospital wide/ward performance-improvement programs with substantial nursing components; 4 rapid-diagnostics studies including 2 randomized trials) met inclusion. Nursing-led protocols consistently reduced time-to antibiotics by 29–60 minutes and were associated with lower in-hospital mortality in several cohorts. Rapid diagnostics reliably shortened time to organism identification and optimal therapy and reduced broad spectrum exposure; mortality effects were mixed. Conclusions: Integrated approaches pairing nursing-led screening and activation with rapid diagnostics reduce treatment delays and can improve antibiotic stewardship; mortality benefits are most evident where programs include empowered nurse activation, streamlined order sets, and stewardship feedback. Hospitals should invest in nurse capacity and workflow integration alongside diagnostics.