In the last years, the oncologic research is focusing on the optimization of the clinical approach to the tumor disease, through the development of new therapeutic strategies combining currently used antineoplastic drugs to targeted delivery systems. In fact, due to the drugs poor selectivity for cancer cells, an highly aggressive style of dosing is necessary to eradicate tumors, causing severe toxicity to normal cells. Therefore, localized drug delivery would, ideally, improve the therapeutic efficacy, minimizing side effects. Mesoporous silica nanoparticles (MSNs) have been proposed as a promising class of versatile drug/DNA delivery vehicles, as well as efficient tools for fluorescent cell tracking. To date, the major limitation is that MSNs enter the cells regardless of a target-specific functionalization. Therefore, this review is aimed to give a brief up to date overview on mesoporous silica based-drug delivery vehicles, specifically applied to tumor therapy, giving particular emphasis to the importance of a targeting function grafted on the carrier surface, so to avoid an indiscriminate uptake by cells.