In nanomedicine, physicochemical properties of the nanocarrier affect the nanoparticle's pharmacokinetics and biodistribution, which are also decisive for the passive targeting and nonspecific cellular uptake of nanoparticles. Size and surface charge are, consequently, two main determining factors in nanomedicine applications. Another important parameter which has received much less attention is the morphology (shape) of the nanocarrier. In order to investigate the morphology effect on the extent of cellular internalization, two similarly sized but differently shaped rod-like and spherical mesoporous silica nanoparticles were synthesized, characterized and functionalized to yield different surface charges. The uptake in two different cancer cell lines was investigated as a function of particle shape, coating (organic modification), surface charge and dose. According to the presented results, particle morphology is a decisive property regardless of both the different surface charges and doses tested, whereby rod-like particles internalized more efficiently in both cell lines. At lower doses whereby the shape-induced advantage is less dominant, charge-induced effects can, however, be used to fine-tune the cellular uptake as a prospective 'secondary' uptake regulator for tight dose control in nanoparticle-based drug formulations.