Background/Objectives: MRI FLAIR signal serves as a time surrogate in unknown onset strokes; however, its prognostic value in early known-onset strokes treated with intravenous thrombolysis (IVT) remains unclear. We aim to evaluate whether FLAIR positivity predicts hemorrhagic transformation and less favorable functional outcome following IVT within 4.5 h of symptom onset. Methods: A systematic search of Embase, PubMed, and Cochrane Library was conducted. We included studies reporting 90-day functional outcome and hemorrhagic transformation after intravenous thrombolysis within 4.5 h of symptom onset in relation to the FLAIR signal on pre-treatment MRI. Two reviewers independently extracted data and assessed bias using QUIPS. A random-effects model was used for meta-analysis. The study protocol was registered in PROSPERO (CRD42023486781). Results: Six studies comprising 951 patients were included in the final analysis. Patients with FLAIR-positive lesions (25.86%) had non-significantly higher odds of hemorrhagic transformation (OR, 3.47; 95% CI, 0.51–23.57; p = 0.131) and significantly higher odds of unfavorable 90-day outcome (OR, 2.14; 95% CI, 1.01–4.55; p = 0.049). The pooled sensitivity and specificity of FLAIR status for predicting hemorrhagic transformation were 41.2% and 82.1%. The pooled sensitivity and specificity of FLAIR status for predicting less favorable outcome were 40.9% and 78.1%, respectively. Conclusions: FLAIR positivity is significantly associated with less favorable 90-day functional outcome and a trend toward a higher rate of hemorrhagic transformation following IVT within 4.5 h of symptom onset. It may aid risk stratification but should not preclude treatment in eligible patients.