Cancer treatment continues to represent a challenge for hospitals due to the complexity and variety of the disease. In many cases, the chemotherapy treatment used is low in efficiency, causing serious side effects such as a decrease in lymphocytes and erythrocytes cells. The objective of this chapter is to demonstrate and explain the main materials used to release drugs in antitumor treatments produced by the sol-gel process. Regarding the results, double-modulated stimuli can increase drug delivery at the target site such as the acidic pH (<4), temperature, and redox potential of SiO2@doxorubicin and SiO2-ZnO@imatibin nanomaterials. Magnetic/optical particles (ZnFe2O4@curcumin) assist in transporting the drug carrier to the target tissue or cell and are activated photonically to release the drugs at the specific location. It is worth mentioning that several factors can affect the release profile of a drug delivery system, such as the nature of the host, the chemical interactions of the components, and the size of the material’s pores possibly due to its small size (<100 nm), which can escape the clearance of the reticuloendothelial system. One of the methods to improve drug delivery with nanomaterials produced by sol-gel is functionalization promoting a better interaction between the carrier, the drug, and the affected cells such as the SiO2@IFC-305 nanostructure functionalized with OH groups. Therefore, the development of new drug storage and release systems by sol-gel process denotes advantages such as greater bioavailability, safety, and efficacy profile; controlled and prolonged release time; and predictable therapeutic response.