Letao Yang^a, Tae‐Hyung Kim^a, Hyeon‐Yeol Cho^a,b, Jeffrey Luo^a, Jong‐Min Lee^c, Sy‐Tsong Dean Chueng^a, Yannan Hou^a, Perry To‐Tien Yin^a, Jiyou Han^d, Jong Hoon Kim^d, Bong Geun Chung^c, Jeong‐Woo Choi^b, Ki‐Bum Lee^a,*

^aDepartment of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 123 Bevier Road, Piscataway, NJ 08854, USA
^bDepartment of Chemical and Biomolecular Engineering, Sogang University, Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea
^cDepartment of Mechanical Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea
^dCollege of Life Sciences and Biotechnology, Science Campus, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02741, Republic of Korea

^*To whom correspondence should be addressed.

Nanoparticle‐based nucleic acid conjugates (NP‐NACs) hold great promise for theragnostic applications. However, several limitations have hindered the realization of their full potential in the clinical treatment of cancer and other diseases. In diagnoses, NP‐NACs suffer from low signal‐to‐noise ratios, while the efficiency of NP‐NACs‐mediated cancer therapies has been limited by the adaptation of alternative prosurvival pathways in cancer cells. The recent emergence of personalized and precision medicine has outlined the importance of having both accurate diagnosis and efficient therapeutics in a single platform. As such, the controlled assembly of hybrid graphene oxide/gold nanoparticle (Au@GO NP)‐based cancer‐specific NACs (Au@GO NP‐NACs) for multimodal imaging and combined therapeutics is reported. The developed Au@GO NP‐NACs show excellent surface‐enhanced Raman scattering (SERS)‐mediated live‐cell cancer detection and multimodal synergistic cancer therapy through the use of photothermal, genetic, and chemotherapeutic strategies. Synergistic and selective killing of cancer cells are then demonstrated using in vitro microfluidic models. Moreover, with the distinctive advantages of the Au@GO NP‐NACs for cancer theragnostics, precision cancer treatment through the detection of cancer cells in vivo using SERS followed by efficient ablation of tumors is shown. Therefore, the Au@GO NP‐NACs can pave a new road for advanced disease theragnostics.