For biomedical applications, mesoporous silica nanoparticles (MSNs)-based theranostic agents have shown to be a promising alternative. Rational design of particulate systems should consider, beside the physicochemical properties of particle size and surface chemistry, shape features as aspect ratio (AR) and morphology. Recent advances of fabrication technologies for manufacturing different shaped MSNs and evaluation means of its in vitro and in vivo biological performance provide new aspects and wisdom in nanomedicine development. In this review, we discussed the recent progress in the preparation of different shaped MSNs and the evaluation of shape-mediated biological effects. Firstly, we provide an overview of preparation strategies for fabricating MSNs with different aspect ratios and different morphologies, including hollow/rattle MSNs, multishell MSNs, and mesoporous silica nanocomposites. We then highlight the aspect ratio- and morphology-mediated biological effects of MSNs respectively. For AR-mediated biological effects of MSNs, we put our focus in the particle ARs effect on cellular uptake, biocompatibility, and drug delivery. For morphology-mediated biological effects of MSNs, we emphasize on how particle shapes could affect tumor therapy. Finally, for application considerations, we conclude with our personal perspectives on the directions in which future studies in this field might be placed.