Engineering tools at the nano-bio interface have enabled transformative advances in molecular diagnostics, therapeutic monitoring, and cellular manipulation. However, challenges remain in achieving continuous real-time sensing, intracellular probing, and controlled actuation within an integrated, multifunctional platform. Nanotechnology, particularly through localized surface plasmons (LSPs), addresses these challenges by leveraging radiative decay for enhanced optical sensing (e.g., SERS) and non-radiative decay for nanoscale actuation (e.g., photothermal effects and vapor nanobubbles). Conventional plasmonic systems, however, are limited in wavelength multiplexing, versatility, and spatial mode overlap. To overcome these shortcomings, this dissertation presents a wavelength-multiplexed multimodal optical nano-bio interfaces enabled by multiresonant plasmonic architectures. These systems combine advanced plasmonic designs with intimate bio-nano interfaces, achieving multifunctionality across a broad spectral range for biochemical sensing and nanoscale actuation. The core platform is built on metal-insulator-metal (MIM) plasmonic nanolaminate nanopillar arrays (NLNPAs), which provide tunable multiresonant responses, nanoscale mode overlap, and an intimate bio-nano interface. For biochemical sensing, the multiband plasmonic resonances enable broadband surface-enhanced Raman scattering (SERS), offering high sensitivity and molecular specificity across a wide spectral range. This capability facilitates high-dimensional molecular fingerprinting, providing insights into spatial-temporal biochemical processes. Additionally, the platform enhances nonlinear optical processes, such as second- and third-harmonic generation (SHG/THG), enabling broadband, label-free sensing and bio-actuation with tunable performance. Beyond sensing, the multiresonant plasmonic interface supports precise nanoscale actuation through femtosecond laser-induced vapor nanobubbles. This approach enables highly localized, minimally invasive membrane permeabilization—optoporation—facilitating intracellular biochemical sensing and molecular delivery with nanoscale precision. Such capabilities hold significant promise for applications in bio-nanophotonics, targeted drug delivery, and cellular biochemical analysis, offering a pathway for advancing molecular diagnostics, minimally invasive therapies, and precise nanosurgery. As a proof-of-concept, a vapor nanobubble-enabled regenerative SERS sensing platform is demonstrated for continuous, wavelength-multiplexed biochemical monitoring. By combining photothermal nanocavitation with plasmonic SERS hotspots, the system achieves ultrasensitive molecular detection in protein-rich biofluids, such as bacterial biofilms associated with chronic wounds. This platform allows real-time monitoring of biochemical evolution in complex biointerfaces, offering a robust tool for continuous molecular fingerprinting in dynamic biological systems. Collectively, these advancements establish the wavelength-multiplexed multimodal optical nano-bio interface as a versatile platform that bridges the gap between nanoscale optical engineering and biological applications. By enabling simultaneous spatial-temporal sensing and actuation with nanoscale precision, this work paves the way for transformative applications in molecular diagnostics, real-time therapeutic monitoring, and cellular biochemical analysis. Future efforts toward portable instrumentation and integration with wearable or implantable technologies will further enhance the platform's potential for non-invasive, real-time monitoring in clinical and healthcare settings, driving forward the future of bio-nanophotonics. / Doctor of Philosophy / The ability to observe, analyze, and control biological processes at the tiniest scales—down to individual cells and molecules— has the potential to transform our understanding of life and revolutionize medicine, diagnostics, and healthcare. Imagine tools that can simultaneously detect disease-related molecules, deliver medicine with pinpoint accuracy, and monitor changes happening inside cells in real time. Achieving this, however, is no small feat. Existing tools often lack the ability to perform multiple tasks at once or adapt to the dynamic nature of living systems. To address this, we developed a new type of nano-bio interface that uses specialized nanostructures to interact with light in unique ways. These tiny structures can trap and amplify light across a wide range of colors, allowing us to achieve multifunctional capabilities at different colors: detecting molecules, probing inside cells, and even triggering specific biological responses using short bursts of laser light. For sensing, the system enhances Raman spectroscopy, a technique that reads the molecular "fingerprints" of chemicals, helping us detect and identify molecules with high precision. For cellular manipulation, we use short laser pulses to generate tiny bubbles that can temporarily open cell membranes—optoporation—enabling drug delivery or accessing the cell's biochemical content without causing harm. Additionally, the system can monitor changes over time, such as the molecular activity within bacterial biofilms, which are responsible for chronic infections. This work opens exciting new possibilities for medicine and biology: detecting diseases earlier, delivering therapies more precisely, and analyzing biological processes in real time. In the future, these nano-tools could be incorporated into portable devices, wearables, or implants, enabling doctors and scientists to monitor health and treat diseases in ways that are faster, safer, and more effective.