A series of four isoreticular MOFs (IRMOF-1, -10, -14, and -16) were selected for a computational investigation of the effect of ligand aromaticity on the adsorption capacity of an aromatic VOC (benzene) compared to its nonaromatic analog (cyclohexane). The affinity of the adsorbates was evaluated by calculating Henry’s constants and adsorption enthalpies. It has been evidenced that while KH values decrease with ligand elongation (IRMOF-10 and -16), inserting a pyrene core into the MOF structure (IRMOF-14) increases both the cyclohexane and benzene adsorption efficiency by ∼290 and 54%, respectively. To elucidate host–guest interactions, we sought to locate preferential adsorption sites in MOF structures for the two VOCs studied by using the GCMC method. It appears that benzene interacts with the metal center (Zn4O clusters) and most of the ligand while cyclohexane tends to localize preferentially only near the Zn4O clusters. Coadsorption isotherms (equimolar mixture of benzene and cyclohexane) demonstrated the preferential adsorption of cyclohexane due to the stronger affinity for the MOF structure. On the other hand, for other isoreticular structures, the ligand elongation leads to a shift of the adsorption curve of cyclohexane caused by pore size increase and therefore less interactions with the walls. This phenomenon is counterbalanced in the case of IRMOF-14 due to stronger interactions between the cyclohexane and pyrene groups. The present results thus open perspectives in the design of promising MOF candidates for high-performing separation and sorption/detection of hydrocarbon VOCs.