BackgroundDistinguishing high‐grade gliomas (HGGs) from brain metastases (BMs) using perfusion‐weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear.PurposeTo compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation.Study TypeSystematic review and meta‐analysis.PopulationTwenty‐four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488).Field Strength/SequenceArterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast‐enhanced (DCE), and dynamic susceptibility contrast‐enhanced (DSCE) sequences at 1.5 T and 3.0 T.AssessmentFollowing the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs.Statistical TestsStandardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I2 statistic was used to assess statistical heterogeneity. A P‐value<0.05 was considered significant.ResultsHGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05–0.69) and CBV (SMD = 0.26, 95% CI: 0.01–0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08).Data ConclusionASL‐derived CBF may be more useful than DSC‐derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible.Level of Evidence1.Technical EfficacyStage 2.