Development of multifunctional nanoparticles (NPs) with desired properties is a significant topic in the field of nanotechnology and has been anticipated to revolutionize cancer diagnosis and treatment modalities. The surface character is one of the most important parameters of NPs that can directly affect their fate, bioavailability, and final theranostic outcomes and thus should be carefully tuned to maximize the diagnosis and treatment effects while minimizing unwanted side effects. Surface engineered NPs have utilized various surface functionality types and approaches to meet the requirements of cancer therapy and imaging. Despite the various strategies, these surface modifications generally serve similar purposes, namely, introducing therapeutic/imaging modules, improving stability and circulation, enhancing targeting ability, and achieving controlled functions. These surface engineered NPs hence could be applied in various cancer diagnosis and treatment scenarios and continuously contribute to the clinical translation of the next-generation NP-based platforms toward cancer theranostics.In this Account, we present recent advances and research efforts on the development of NP surface engineering toward cancer theranostics. First, we summarize the general strategies for NP surface engineering. Various types of surface functionalities have been applied including inorganic material-based functionality, organic material-based functionality like small molecules, polymers, nucleic acids, peptides, proteins, carbohydrates, antibodies, etc., and biomembrane-based functionality. These surface modifications can be realized by prefabrication or postfabrication functionalization, driven by covalent conjugations or noncovalent interactions. Second, we highlight the general aims of these different NPs surface functionalities. Different therapeutic and diagnostic modules, such as nanozymes, antibodies, and imaging contrast agents, have been modified on the surface of NPs to achieve theranostic function. Surface modification also can improve stability and circulation of NPs by protecting the NPs from immune recognition and clearance. In addition, to achieve targeted therapy and imaging, various targeting moieties have been attached on the NP surface to enhance active targeting ability to tissues or cells of interest. Furthermore, the NP surfaces can be tailored to achieve controlled functions which only respond to specific internal (e.g., pH, thermal, redox, enzyme, hypoxia) or external (e.g., light, ultrasound) triggers at the precise action sites. Finally, we present our perspective on the remaining challenges and future developments in this significant and rapidly evolving field. We hope this Account can offer an insightful overlook on the recent progress and an illuminating prospect on the advanced strategies, promoting more attention in this area and adoption by more scientists in various research fields, accelerating the development of NP surface engineering with a solid foundation and broad cancer theranostics applications.