Background: Time-to-positivity (TTP) of blood cultures reflects pathogen burden and growth kinetics and has been proposed as a prognostic indicator in bloodstream infections (BSIs). However, the extent to which TTP predicts clinical outcomes remains uncertain. Objectives: To systematically evaluate the association between TTP and adverse clinical outcomes, including mortality, illness severity, ICU admission, and persistent bacteremia. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception to June 2025. Observational and interventional studies reporting outcomes stratified by TTP were included. Risk of bias was assessed using the Newcastle–Ottawa Scale, and random-effects models were applied for pooled analyses. Results: Twenty-three studies comprising diverse adult and pediatric cohorts were included. Shorter TTP (commonly <12–24 h) was consistently associated with higher in-hospital mortality, greater illness severity, ICU admission, and persistent bacteremia, with the strongest associations observed in Staphylococcus aureus bacteremia and candidemia. Findings in Gram-negative bacteremia were more heterogeneous, reflecting variation in host and pathogen characteristics. Heterogeneity across studies was moderate and largely attributable to differences in TTP thresholds and clinical adjustment methods. Conclusion: Shorter TTP is a clinically meaningful prognostic marker in BSIs and may support early risk stratification when interpreted alongside clinical context. Standardized TTP thresholds and prospective multicentre validation are required before routine integration into prognostic pathways.