Elevated intracranial pressure (ICP) with reduced cerebral perfusion pressure is a well-known cause of secondary brain injury. Previously, there have been some reports describing different supra- and infratentorial ICP measurements depending on the location of the mass effect. Therefore, we aimed to perform a systematic review and meta-analysis to clarify the issue of optimal ICP monitoring in the infratentorial mass lesion. A literature search of electronic databases (PUBMED, EMBASE) was performed from January 1969 until February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Two assessors are independently screened for eligible studies reporting the use of simultaneous ICP monitoring in the supra- and infratentorial compartments. For quality assessment of those studies, the New Castle Ottawa Scale was used. The primary outcome was to evaluate the value of supra- and infratentorial ICP measurement, and the secondary outcome was to determine the time threshold until equalization of both values. Current evidence surrounding infratentorial ICP measurement was found to be low to very low quality according to New Castle Ottawa Scale. Eight studies were included in the systematic review, four of them containing human subjects encompassing 27 patients with infratentorial pathology. The pooled data demonstrated significantly higher infratentorial ICP values than supratentorial ICP values 12 h after onset (p < 0.05, 95% CI 3.82–5.38) up to 24 h after onset (p < 0.05; CI 1.14–3.98). After 48–72 h, both ICP measurements equilibrated showing no significant difference. Further, four studies containing 26 pigs and eight dogs showed a simultaneous increase of supra- and infratentorial ICP value according to the increase of supratentorial mass volume; however, there was a significant difference towards lower ICP in the infratentorial compartment compared to the supratentorial compartment. The transtentorial gradient leads to a significant discrepancy between supra- and infratentorial ICP monitoring. Therefore, infratentorial ICP monitoring is warranted in case of posterior fossa lesions for at least 48 h.