Nanobiotechnology rapidly progresses to use nanostructures, improving the effectiveness of cytotoxic agents for optimal anticancer results. In comparison to other nanostructures, organic nanomaterials (NMs) are convenient for successfully delivering cytotoxic substances to cancer or tumor cells due to their superior blood circulation time, high tropism against cancer cells, high cellular uptake, biocompatibility, and biodegradability. However, these features can be tuned by rationally designing them to respond against stimuli that mimic the molecular and cellular conditions found within in vitro and in vivo cancer cell models. This chapter is focused on recent scientific evidence regarding the use of organic NMs such as polymeric nanoparticles, liposomes, micelles, dendrimers, and virus-like particles (VLPs) to deliver cytotoxic drugs within cancer cell lines and xenograft models to treat distinct types of cancer. The processes regarding their synthesis, characterization, and evaluation to entrap and deliver anticancer molecules such as alkylating agents (doxorubicin), anti-tubulin drugs (paclitaxel), and natural products (vitamin E and quercetin) were reviewed, as well as their activity against lung, breast, colon, and pancreatic cancer models. The fundamentals behind each process are covered and illustrative examples are provided. Regarding their design, their capacity to respond toward conditions that simulate carcinogenic phenomena was included. Future approaches are required to determine the capacity of organic NMs to deliver other cytotoxic drugs and their safe performance against in vitro and in vivo cancer models.