A novel mixed-signal adaptable silicon-based coherent photoacoustic (PA) sensing system-on-chip (SoC) is proposed to detect various kinds of target signals robustly under high noise and strong interferences in compact chip-level, attaining precise in vivo sensing for physiological signs monitoring and enhanced bio-imaging. Based on the configurable coherent PA sensing SoC architecture supported by on-chip Gilbert cell-based multiplier, a digital processing module, and DACs, in-phase (I) and quadrature (Q) templates generated by digital module on-chip are configurable to be with a high correlation coefficient to the target PA signal, attaining detection and reconstruction of target signals in a coherent detection mode. The correlation between the received PA signal and the templates is implemented efficiently, assuring accurate tracking and precise reconstruction on the target PA signals at the chip level. Based on the integrated PA SoC fabricated by the TSMC 65-nm CMOS process, precise in vivo sensing and imaging can be assured at the edge. Further, as PA detection leverages optical and ultrasound sensing, in vivo imaging on in-depth vessels or other tissues can be attained. The mixed-signal PA SoC paves the way for sustainable health monitoring and owns immense potential for early disease diagnostics based on in vivo blood temperature sensing and vessel imaging.