Abstract Theranostic system combined diagnostic and therapeutic modalities is critical for the real‐time monitoring of disease‐related biomarkers and personalized therapy. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. They have shown attractive properties including painless skin penetration, easy self‐administration, prominent therapeutic effects, and good biosafety. Herein, an overview of the microneedles‐based diagnosis, therapies, and theranostic systems is given. Four microneedles‐based detection methods are concluded based on the sensing mechanism: i) electrochemistry, ii) fluorometric, iii) colorimetric, and iv) Raman methods. Additionally, robust microneedles are suitable for implantable drug delivery. Microneedles‐assisted transdermal drug delivery can be primarily classified as passive, active, and responsive drug release, based on the release mechanisms. Microneedles‐assisted oral and implantable drug delivery mechanisms are also presented in this review. Furthermore, the key frontier developments in microneedles‐mediated theranostic systems as the major selling points are emphasized in this review. These systems are classified into open‐loop and closed‐loop theranostic systems based on the indirectness and directness of feedback between the transdermal diagnosis and therapy, respectively. Finally, conclusions and future perspectives for next‐generation microneedles‐mediated theranostic systems are also discussed. Taken together, microneedle‐based systems are promising as the new avenue for diagnosis, therapy, and disease‐specific closed‐loop theranostic applications.