This chapter, titled “Advanced Optoelectronic Approaches in SpO₂ Measurement Systems,” provides an in-depth analysis of pulse oximetry technology, extending from biophysical principles to advanced hardware control. It highlights critical limitations in current devices, specifically “occult hypoxemia,” where racial bias in calibration algorithms causes dangerous overestimation of oxygen levels in darkskinned individuals due to melanin interference. Distinct from simulation-based studies, the authors utilize a “Hardware-in-the-Loop” laboratory testbench featuring a dynamic tissue phantom to replicate real-world optical scattering and circulatory conditions. The research comparatively evaluates classical PID control versus an Artificial Neural Network (ANN) for regulating LED current. Experimental results demonstrate that the ANN controller significantly outperforms the PID method; while the PID controller exhibited varying instability and a high overshoot of 28.51%, the ANN achieved zero overshoot, superior noise rejection, and effective motion artifact suppression. The study concludes that integrating AI-driven control and spectral analysis is essential to ensure equitable clinical accuracy across all skin tones.