Rapid growth in bionanotechnologies towards the improvement of therapeutic strategies against cancer relies on the development of nanomedicine products, such as nanoparticles (NPs). NPs have enormous therapeutic potential for treating tumors, as they represent a way of preparing multi-functionality platforms, achieving sophisticated targeting strategies, enhancing drug delivery, attenuating drug toxicity on healthy organs, and protecting drugs from rapid clearance. Lately, the incorporation of multi-functional theranostic nanocarriers is allowing the simultaneous diagnosis and therapy of cancer, in conjunction with the co-delivery of drugs for combination therapies. However, challenges in the development of optimized NPs have to be addressed; their toxicological characterization, in terms of biocompatibility and immunogenicity, and their targeting selectivity are current limitations to overcome, to fulfill safety requirements and enhance site-specific delivery.