Metal–organic framework (MOF) nanoparticles are promising carriers for the internal delivery of therapeutics to the cells; however, the effects of their shape on cellular uptake have not yet been clearly evaluated. Therefore, we synthesized biocompatible Fe-based MOF nanoparticles of two distinct shapes—rods and octahedrons (NH₂-MIL-88B(Fe)-ROD and NH₂-MIL-88B(Fe)-OCTA, respectively)—and evaluated their cellular uptake kinetics and mechanisms using three different cell lines (HeLa, MDA-MB-231, and L929). Although both nanoparticles possessed the same constituent metal, organic linkers, and thus, crystalline structures, a more rapid uptake was observed with NH₂-MIL-88B(Fe)-OCTA, whereas NH₂-MIL-88B(Fe)-ROD were endocytosed in a more sustained manner. This could be ascribed to the large number of sharp edges available in NH₂-MIL-88B(Fe)-OCTA particles; hence, there were more points of expedited entry into the cells via a clathrin-mediated pathway. The findings herein provide important information for the application of the MOF nanoparticles as intracellular drug delivery carriers, especially when they can be prepared in different shapes with the same composition.