Peptide–drug conjugates that self-assemble into supramolecular nanomaterials have promise for uses in drug delivery. These discrete molecular species offer high and precise drug loading, affording efficient carriers for various therapeutic agents. Their peptide modules, meanwhile, enable biological targeting and stimuli-responsive function while also ordering the assembled nanostructure. The often hydrophobic drug payload likewise acts as a directive for self-assembly in aqueous media. Though accessible synthetic methods have allowed for extensive exploration of the peptide design space, the specific contributions of the drug molecule and its linker to the resulting assembly have been less explored. Hydrophobic drugs frequently have planar domains, conjugated π-systems, and isolated polar groups, which in turn can lead to specific and directional self-interactions. These energies of interaction affect the free energy landscape of self-assembly and may impact the form and assembly process of the desired nanomaterial. Here, two model supramolecular peptide–drug conjugates (sPDCs) are explored, composed of the corticosteroid dexamethasone conjugated to a conserved peptide sequence via two different linker chemistries. The choice of linker, which alters the orientation, rotational freedom, and number of stereoisomers of the prodrug in the final sPDC, impacts the mechanism and energetic barrier of assembly as well as the nano/macroscale properties of the resultant supramolecular materials. Accordingly, this work demonstrates the nonzero energetic contributions of the drug and its linker to sPDC self-assembly, provides a quantitative exploration of the sPDC free energy landscape, and suggests design principles for the enhanced control of sPDC nanomaterials to inform future applications as therapeutic drug carriers.