High-precision in vivo therapeutic technologies that establish three-dimensional (3D), multimodal neural interfaces with targeted biotissues offer significant clinical potential for the timely treatments of localized peripheral nerve injury (PNI). Current approaches for this purpose such as implantable devices face challenges in terms of percutaneous wires and/or nondegradable designs, and support only single-mode operation that lack microscale spatial resolution. Here, we develop a miniaturized, self-wrapping system that yields wireless, multimodal neural interfaces with 3D adaptation across localized peripheral nerves at scales ranging from tens of micrometers (15 μm) to millimeters. Such platform integrates multilayer architectures that include SiN x layers as the mechanically triggered substrate for 3D wrapping, with multimodal treatments via MXene and drug-loaded layers for photothermal stimulation and pharmacological release. Experimental and computational studies establish operational principle as the basis for the combination of long-term photothermal therapy and transient drug delivery at high spatiotemporal resolution. In vivo tests on living rat models demonstrate that the implantable neural interface can roll up across the localized, dynamic surface of injured nerves, providing sustained treatments over 1 mo in a fully bioresorbable design after the healing process. These findings create future opportunities of such wireless, multimodal system with 3D self-wrapping techniques for precise PNI therapeutic strategies.