Current biosensors have limited application in clinical diagnostics as they lack the high order of specificity needed to detect low molecular analytes, especially in complex fluids (such as blood, urine, and saliva). In contrast, they are resistant to the suppression of non-specific binding. Hyperbolic metamaterials (HMMs) offer highly sought- after label-free detection and quantification techniques to circumvent sensitivity issues as low as 105M concentration in angular sensitivity. This review discusses design strategies in detail and compares nuances in conventional plasmonic techniques to create susceptible miniaturized point-of-care devices. A substantial portion of the review is devoted to developing low optical loss reconfigurable HMM devices for active cancer bioassay platforms. A future perspective of HMM-based biosensors for cancer biomarker detection is provided.