The toxic paradigms of chemotherapeutic drugs and nanoparticles are tightly linked. Whereas uncontrolled exposure of living systems to therapeutics/nanomaterials leads to toxicity, selective induction of cytotoxicity in cancer cells helps in the fight against cancer. The increasing understanding of nanotoxicity paradigms has recently resulted in important benchmarks for the safe design of nanomaterial-based drug delivery systems aiming to fight cancer. In this context, this review aims to compile and present recent advances, outcomes and interconnections between nanomaterial-based drug delivery and nanotoxicity disciplines in order to provide a comprehensive guidance for future research. First, the basic concepts and mechanisms of nanomaterial-based drug delivery and nanotoxicity are introduced. Second, we present a detailed classification of drug delivery strategies and nanotoxicity paradigms, supported by the most recent research studies with a special focus on the interconnections between nanotoxicity and drug delivery research, which are highlighted in order to explore future opportunities for developing advanced therapeutic approaches. Finally, this review is concluded with future prospects on the use of nanoparticles for manipulating the behavior of cells and animals.