Metal-organic frameworks (MOF) and covalent organic frameworks (COFs) are promising nanocarriers for targeted drug delivery. For their uptake and release, non-covalent interactions between the framework and the drugs play a fundamental role. However, an in-depth understanding of how different functional groups affect these interactions is still lacking. Using a multilevel approach combining molecular docking and density functional theory, we show in the publication associated with this data how computational modeling can be exploited to gain information on the interplay between functionalization and drug delivery features. We find that functional groups significantly impact the strength of the host-guest interactions. Moreover, the interaction strength qualitatively correlates with drug release data from experimental literature, providing a link between framework structure and release properties. The results of our study facilitate the customization of non-covalent interactions between MOFs/COFs and drugs and give direction on how to rationally design nanocarriers for sustaining the drug release in the body over longer times. The data deposited on the Materials Cloud Archive contains the inputs and outputs of the molecular docking and DFT simulations.