Flexible microinterventional sensors represent a transformative technology that enables the minimal intervention required to access and monitor complex biosignals (e.g., bioelectrical, biophysical, and biochemical signals) originating from deep tissues, thereby providing accurate data for diagnostics, robotics, prosthetics, brain-computer interfaces, and therapeutic systems. However, fully unlocking their potential hinges on establishing a nondisruptive, intimate, and nonrestrictive interface with the tissue surface, facilitating efficient integration between the microinterventional sensor and the target tissue. In this comprehensive review, we highlight the critical tissue characteristics in both physiologically and pathologically relevant contexts that are pivotal for the design of microinterventional sensors. We also summarize recent advancements in flexible substrate materials and conductive materials, which are tailored to facilitate effective information interaction between bioelectronic components and biological tissues. Furthermore, we classify various electrode architectures─spanning 1D, 2D, and 3D─designed to accommodate the mechanics of soft tissues and enable nonrestrictive interfaces in diverse sensing scenarios. Additionally, we outline critical challenges for next-generation microinterventional sensors and propose integrating advanced materials, innovative fabrication, and embedded intelligence to drive breakthroughs in biosignal sensing. Ultimately, we aim to both provide foundational understanding and highlight emerging strategies in biosignal capture, leveraging recent advancements in these critical components.