Anti-cancer conventional chemotherapeutic drugs novel formula progress, nowadays, uses nano technology for targeted drug delivery, specifically tailored to overcome therapeutic agents’ delivery challenges. Polymer drug delivery systems (DDS) play a crucial role in minimizing off-target side effects arising when using standard cytotoxic drugs. Using nano-formula for targeted localized action, permits using larger effective cytotoxic doses on a single special spot, that can seriously cause harm if it was administered systemically. Therefore, various nanoparticles (NPs) specifically have attached groups for targeting capabilities, not seen in bulk materials, which then need activation. In this review, we will present a simple innovative, illustrative, in a cartoon-way, enumeration of NP anti-cancer drug targeting delivery system activation-types. Area(s) covered in this review are the mechanisms of various NP activation techniques.