Cutting-edge biological and medical research demands innovative methods for sensing and modulating complex tissues, organs, and organ systems. Recent progress in bioelectronics enables multimodal interfacing for broad fundamental and therapeutic applications. However, key challenges persist in interfacing with complex biological geometries, particularly for applications requiring conformal contact in electrical, chemical, or mechanical biointerfaces. In this talk, I will introduce our work on three-dimensional biointerfaces to address this challenge. These 3D biointerfaces feature precisely programmable geometries and/or ultrasoft nature that enable conformal contacting with multiscale tissues and organs. The first part of the talk focuses on our work in full-surface 3D interface for 3D-shaped neural organoids. These 3D programmable frameworks enable nearly complete surface accessibility of neuronal populations for the first time. They support high-resolution recording and stimulation via hundreds of individual channels and allow for 3D reconstruction for spatial electrophysiology. These capabilities enable monitoring 3D network-level neural activities, supporting broad biological and medical research as demonstrated with neural activity manipulation, pharmacological studies, and modeling neural disease phenotypes. Next, I will discuss our work on organ interface. We develop hydrogel-based ultrasoft thin platforms that enable real-time pH sensing. These platforms integrate ultrasound imaging for deep tissue monitoring, and address the long-standing clinical challenge of early detection of gastrointestinal (GI) system leakage after surgery. In the last part of the talk, I will present our work on novel nanofabrication techniques for large scale and aligned 3D nanostructured surfaces which match the scale of cellular and subcellular sensing. Together, these works open new possibilities for precision engineering of advanced bioelectronics with 3D features that allow sufficient interfacing with complex geometries, enabling transformative applications in organoid research and neural engineering, precision medicine, and spatial characterization platforms for complex in vitro and in vivo biological systems for advanced medical and therapeutic applications.