<p>Monoliths are versatile materials with diverse applications, and their performance can be enhanced through modifications, including the use of metal–organic frameworks (MOFs). Modified monoliths improve separation and analytical processes in various fields, with different modification methods offering distinct benefits and challenges. Directly adding MOF crystals to the polymerization mixture is straightforward and time effective, but it often results in poor dispersion and compositional heterogeneity, which compromises consistency and reproducibility, particularly in bioanalytical applications. Although layer-by-layer (LbL) development or post-synthesis functionalization provides greater control over surface coverage and layer thickness, improving selectivity, it is challenging and complicated, making it less appropriate for scalable or high-throughput applications. Despite these challenges, MOFs’ capabilities are enhanced by their incorporation into monolithic structures, which provide better performance, efficiency, and selectivity. These hybrid materials have a lot of potential for use in pharmaceutical development, environmental monitoring, and biomolecule enrichment. However, concerns like material heterogeneity, reproducibility, and scalability limit their practical application in bioanalysis.</p> Graphical Abstract <p></p>