In situ spatiotemporal characterization of correlated bioelectrical and biochemical processes in living multicellular systems remains a formidable challenge but can offer crucial opportunities in biology and medicine. A promising approach is to develop bio-interfaced multifunctional micro-/nano-sensor arrays with complementary biophotonic–bioelectronic modalities and biomimetic topology to achieve combined bioelectrical and biochemical detection and tight device-cell coupling. However, a system-level engineering strategy is still missing to create multifunctional micro-/nano-sensor arrays that meet the multifaceted design requirements for in situ spatiotemporal characterizations of living systems. Here, we demonstrate a hierarchical modular design and fabrication approach to develop scalable two-tier protruding micro-/nano-optoelectrode arrays that extend the design space of biomimetic micro-/nano-pillar topology, plasmonic nanoantenna-based biophotonic function in surface-enhanced Raman spectroscopy (SERS), and micro-/nano-electrode-based bioelectronics function in electrochemical impedance spectroscopy (EIS). Notably, two-tier protruding micro-/nano-optoelectrode arrays composed of nanolaminate nanoantenna arrays on top of micropillar electrode arrays can support plasmonic nanocavity modes with high SERS enhancement factors (≈10⁶) and large surface-to-volume ratio with significantly reduced interfacial impedance in EIS measurements. We envision that scalable two-tier protruding micro-/nano-optoelectrode arrays can potentially serve as bio-interfaced multifunctional micro-/nano-sensor arrays for in situ correlated spatiotemporal bioelectrical-biochemical measurements of living multicellular systems such as neuronal network cultures, cancerous organoids, and microbial biofilms.