Reproducibility in the synthesis of complex materials such as metal–organic frameworks (MOFs) remains a major challenge. Under seemingly identical experimental conditions, a distribution of MOF crystals with different structural properties is obtained, resulting in a heterogeneous performance. For quality assurance, analytical techniques and protocols are needed to predict MOF crystal quality already during the synthesis process. In this work, in situ Raman spectroscopy is used to monitor the formation of 2D phthalocyanine-based MOFs at the air–water interface. Raman marker bands are identified that visualise the competing processes of linker aggregation and MOF formation. Using transmission electron microscopy (TEM) measurements on the MOF crystals after synthesis, a correlation between the Raman marker bands and the resulting crystalline domain size distribution of the MOF can be derived. This noninvasive, fast, and simple in situ quality assessment method marks a significant step toward automated MOF synthesis.