Core-shell nanoparticles (CSNPs) have emerged as powerful tools for biological oxygen sensing due to their exceptional structural and functional properties. These nanoparticles, designed with a functional core and protective shell, enhance dispersibility, biocompatibility, and cytocompatibility, making them particularly suitable for intracellular and targeted oxygen sensing. Ruthenium and porphyrin complexes, commonly used as fluorescent and phosphorescent probes, are frequently encapsulated within CSNPs to enable precise fluorescence lifetime-based oxygen measurements. Inclusion of these dyes in polymers or shells offers several advantages, such as preventing dye leaching into tissues, mitigating singlet oxygen toxicity, enabling targeted sensing of cells or organelles, and extending probe lifetime. This paper demonstrates the use of fluorescence lifetime measurements in the time-domain approach, leveraging a multi-channel scaler, to evaluate oxygen levels. Additionally, it discusses CSNPs incorporating Ru and porphyrin dyes from three perspectives: (a) preparation methods, (b) spectroscopic characteristics, and (c) biomedical applications. Overall, CSNPs provide a versatile and efficient platform for realtime monitoring of oxygen levels, with significant potential in biomedical and biophysical research.This paper explores the design strategies, mechanisms, and potential of core-shell nanoparticles in advancing the field of biological oxygen sensing.