Personalized medicine transforms healthcare by adapting interventions to individuals’ unique genetic, molecular, and clinical profiles. To maximize diagnostic and/or therapeutic efficacy, personalized medicine requires advanced imaging devices and sensors for accurate assessment and monitoring of individual patient conditions or responses to therapeutics. In the field of biomedical optics, short-wave infrared (SWIR) techniques offer an array of capabilities that hold promise to significantly enhance diagnostics, imaging, and therapeutic interventions. SWIR techniques provide in vivo information, which was previously inaccessible, by making use of its capacity to penetrate biological tissues with reduced attenuation and enable researchers and clinicians to delve deeper into anatomical structures, physiological processes, and molecular interactions. Combining SWIR techniques with machine learning (ML), which is a powerful tool for analyzing information, holds the potential to provide unprecedented accuracy for disease detection, precision in treatment guidance, and correlations of complex biological features, opening the way for the data-driven personalized medicine field. Despite numerous biomedical demonstrations that utilize cutting-edge SWIR techniques, the clinical potential of this approach has remained significantly underexplored. This paper demonstrates how the synergy between SWIR imaging and ML is reshaping biomedical research and clinical applications. As the paper showcases the growing significance of SWIR imaging techniques that are empowered by ML, it calls for continued collaboration between researchers, engineers, and clinicians to boost the translation of this technology into clinics, ultimately bridging the gap between cutting-edge technology and its potential for personalized medicine.