The surge of pathogenic illnesses is responsible for millions of mortalities occurring in underdeveloped and developing countries. Different pathogens such as viruses, bacteria, fungi, and protozoa are the causative agents of fatalities. The rapid proliferation of pathogenic diseases threatens the entire human population and possibly the economy. Owing to the time-consuming and sophisticated laboratory setup, conventional diagnostic tools are not sufficient for the detection of microbial infections. To treat pathogenic infections successfully, simple, fast, accurate, and cost-effective detection tools are of great importance. Optical biosensors are effective techniques for the highly sensitive, specific, multiplexed, and easy-to-use techniques for the determination of microbial infections. In the modern era, the need for efficacious point-of-care (POC) diagnostic techniques is in huge demand with the prominence of portability, high sensitivity, being rapid and user-friendly, and having on-site detection ability. Currently, efforts have been made to the advancement of POC optical biosensors through the integration of technical support like artificial intelligence, machine learning, internet-of-things, and internet-of-medical-things (IoMT). These smart technique-incorporated advanced POC optical biosensors can fill the gap between the generation of bioinformatics, large data analytics, and clinical validation. Moreover, integrated advanced POC optical biosensors will be beneficial to understand the progression of the diseases, clinical authentication, and assessment of the efficiency of the prescribed treatment.