The biomedical research community is looking for non-invasive diagnostic tools for early screening, diagnosis, prognosis prediction, early relapse detection, and follow-up of cancer diseases. In this context, Liquid Biopsy (LB) is emerging as a new minimally invasive diagnostic method that allows reliable analysis and diagnosis of diseases, mainly cancerous diseases, from several biological fluids instead of a fragment of cancer tissue. The capability of performing LB using Lab-On-Chip (LOC) technologies allows for minimizing the invasiveness and risks of tissue biopsy. Here, we review LOCs, designed to achieve a system for personalized medicine capable of performing detection, capture, and analysis of liquid cancer biomarkers (ctDNA, cfDNA, CTCs, exosomes, EVs, etc.). The overview is focused on the photonic sensing section that could ensure high specificity and sensitivity of the system to a selected biomarker and remarkable limit-of-detection (LOD). We provide an overview of biosensor technologies for Personalized Medicine applications, critical and comprehensive evaluations regarding the prospects of the LOC operating platform, and optimization methods for its future applications.