Abstract: In recent years, modified new chemical drugs have gradually become an important focus in the field of innovative drug research in China. Since the registration classification reform in 2016, the number of modified new drugs based on new dosage forms, new indications, and new combinations has been increasing year by year. This not only provides important solutions to unmet clinical needs but also drives enterprises to gradually change their research and development concepts and improve their technical capabilities. By investigating the relevant regulatory requirements for U.S. 505(b)(2) and China’s modified new chemical drugs registration, this article deeply analyzes the similarities and differences between China and the U.S. in terms of recognition standards, data citation, and other aspects. The article also offers some thoughts on the optimization and refinement of relevant key technical points, aiming to provide ideas and references for the project-establishment as well as research and development of modified new drugs.