Over four decades, point-of-care (POC) technologies and their pivotal applications in the biomedical arena have increased irrepressibly and allowed to realize the potential of portable and accurate diagnostic strategies. Today, in the light of these advances, POC systems dominate the medical inventions and bring the diagnostics to the bedside settings, potentially minimizing the workload in the centralized laboratories, as well as remarkably reducing the associated-cost and time. In contrast to the conventional technologies, microfluidics paves the way to create more efficient and applicable POC diagnostic devices through their inherent fashions such as minute volume of samples, easy manipulations, shorter assay time, and low-cost production. In this review, the current status and advancements of microfluidic systems along with the current limitations in the aspect of POC diagnostic strategies are elaborated. Further, the integration of novel materials and innovative sensing platforms to the microfluidic systems are comprehensively evaluated to address the real-world challenges for diagnosing various maladies at the POC settings.