<p>A compact metal–insulator–metal (MIM) plasmonic sensor based on a single Fano resonance is proposed and numerically optimized for high-performance refractive index (RI) sensing and blood plasma concentration (PC) detection. The sensing structure consists of a semicircular resonator coupled to a waveguide and a semi-elliptical cavity, forming a simplified configuration that supports Fano interference without relying on multi-resonator or multichannel architectures. Finite-difference time-domain (FDTD) simulations demonstrate a high RI sensitivity of 452.94&#xa0;nm/RIU, a figure of merit of 50 RI⁻¹, and an ultra-low detection limit of 2.21 × 10^–5 RIU at a spectral resolution of 0.01&#xa0;nm. Despite its structural simplicity, the proposed sensor achieves a modified figure of merit of 2.729, indicating competitive performance compared with recently reported Fano-based MIM sensors. The sensor exhibits a linear spectral response, enabling precise detection of small RI variations relevant to biomedical diagnostics. For blood plasma analysis, a direct sensing approach is employed, yielding a plasma concentration sensitivity of 0.2751 (nm·L)/g over a realistic concentration range, addressing limitations of previous studies based on impractical concentration assumptions. The proposed platform combines simplicity, linearity, and high sensitivity, making it a promising candidate for integrated lab-on-chip blood plasma biosensing applications.</p>