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Photoacoustic imaging is an emerging imaging modality whereby pulsed laser illuminationgenerates pressure transients that are detectable using conventional ultrasound. Plasmonic nanoparticles such as gold nanorods and spheres are commonly employed exogenous contrast agents for both sensing and therapeutic applications. This dissertation first presents a detailed review of engineering plasmonic nanoparticles for enhanced photoacoustic imaging followed by the design of iodide and chalcogenide doped silver-coated gold nanorods for oxidative stress sensing and enhanced photoacoustics. Clinically, photoacoustics leverages hemoglobin and melanin as endogenous contrast agents for breast, vascular, and wound imaging. The rest of this dissertation focuses on the use of ultrasound and photoacoustic imaging to monitor and predict chronic wound healing in human subjects. Chronic wounds are a major health problem that cause the medical infrastructure billions of dollars every year. Chronic wounds are often difficult to heal xxii and cause significant discomfort. Although wound specialists have numerous therapeutic modalities at their disposal, tools that could 3D-map wound bed physiology and guide therapy do not exist. Visual cues are the current standard but are limited to surface assessment; clinicians rely on experience to predict response to therapy. Photoacoustic imaging can solve these major limitations. Chronic wound patients often receive skin grafts to promote tissue regeneration, but grafting makes it impossible to monitor the underlying wound bed. Ultrasound imaging can be used to size wounds in three dimensions, monitor, and predict tissue loss or regeneration under a skin graft. The addition of photoacoustic imaging allows functional imaging of angiogenesis and perfusion into the wound bed, both essential for wound healing. An increase in photoacoustic signal corresponds to higher perfusion and the rate of photoacoustic signal increase can predict if a wound is likely to heal or not. Clinical photoacoustic imaging can be limited by melanin, a major optical absorber giving skin its characteristic color. Subjects with darker skin tones and hence high melanin content absorb more photons leaving less light to probe deeper tissues of interest. The bias against darker skin tones subjects can be easily minimized by designing tools that account for variable melanin concentrations.