Nanoparticle (NP)-mediated therapies are promising tools for the treatment of a wide range of diseases, including stroke and cancer, due to the outstanding performance they have shown for specifically targeting diseased sites. Importantly, the coupling of stiffness and shape of NPs has a significant influence on transportation via blood flow and internalization by targeted cells. Nevertheless, the underlying mechanism of this coupling effect on the endocytosis of NPs remains largely unexplored, resulting from a lack of clear measurement of stiffness for NPs in experiments, as well as the complexity of the endocytosis process. To overcome the above challenges, coarse-grained simulations, which can provide abundant nanoscale details and precise control of mechanical properties of NPs, were implemented to study the stiffness and shape dependence of the endocytosis of spherocylindrical NPs. To understand the coupling effect between shape and stiffness of NPs for membrane wrapping, coarse-grained molecular dynamics (CGMD) models with explicit bond, area, volume, and bending stiffness control were constructed for spherocylindrical NPs with identical volumes but different aspect ratios (ARs) ranging from 1.3 to 11.0. Results indicate that the endocytosis time of NPs increases as the aspect ratio increases due to both the increasing surface area and decreasing wrapping rate resulting from the decreasing contact perimeter. Moreover, soft and long NPs with AR = 11.0 exhibit wormlike wiggling in contrast to rodlike penetration of the stiff, enlarging the contact area and facilitating the endocytosis process. In addition, three types of NP fates are differentiated: full endocytosis, full endocytosis with membrane damage, and partial endocytosis with membrane damage. Among those patterns, damages/defects on the membrane can promote wrapping of NPs, although extra time is needed to close the defect after endocytosis. In summary, our results help gain a deeper understanding of the underlying mechanism of endocytosis of NPs with respect to geometry and particle stiffness, providing a useful guideline for designs of nanoparticles that can be implemented in next-generation nanoparticle-assisted therapy.