Excessive　production　of　oxidative　species　alters　the　normal　redox　balance　and　leads　to　diseases,　such　as　chronic　inflammation　and　cancer.　Oxidative　species　are　short-lived　species,　which　makes　direct,　precise,　and　real-time　measurements　difficult.　Herein,　we　report　a　novel　core–satellite　gold　nanostructure　for　dual,　ratiometric　surface-enhanced　Raman　scattering　(SERS)　and　photoacoustic　(PA)　imaging　to　enable　the　precise　detection　of　inflammation/cancer-related　H2O2.　The　combination　of　H2O2-activated　second　near-infrared　(NIR-II)　PA　imaging　and　SERS　imaging　enables　the　differentiation　between　the　inflamed　region　and　normal　tissue　with　high　accuracy.　The　mesoporous　silica　shell　of　the　nanoprobe　could　be　used　to　deliver　drugs　to　the　target　area　to　precisely　treat　disease.　Therefore,　this　core–satellite　nanostructure　can　not　only　quantitatively　and　precisely　monitor　H2O2　produced　in　inflammation,　tumor,　and　osteoarthritis　in　rabbits　in　real-time,　but　can　also　be　used　to　track　the　progress　of　the　anti-inflammatory　treatment　in　real-time.　©　2020　Wiley-VCH　GmbH