Drug combinations have been widely used in cancer treatment. However, it remains a formidable challenge to deliver three or more therapeutic agents in one nanoparticle with a precise and tunable molar ratio because of differences in pharmacokinetics and biodistribution of various anticancer drugs. Herein, we reported a facile approach to construct ternary cocktail nanoparticles, which are composed of three different anticancer drugs, such as gemcitabine, chlorambucil, and irinotecan, through the molecular coassembly of two amphiphilic drug-drug conjugates. The component of these nanoparticles can be simply adjusted by changing the feed ratio of two amphiphilic drug-drug conjugates in the coassembly process. Without the help of any drug carriers, they can self-deliver, release three drugs synchronally, and obtain the optimal synergistic therapeutic effect. This facile strategy may open a new way for cancer combination therapy.