The convergence of biological microelectromechanical systems (bio-MEMS) and very-large-scale integration (VLSI) circuits represents a paradigm shift in medical technology, enabling the development of miniaturized, sensitive, and intelligent systems for point-of-care diagnostics, continuous health monitoring, and personalized medicine. Bio-MEMS devices act as transducers, converting biological events—such as molecular binding, cellular activity, or chemical changes—into minute mechanical or electrical signals. However, these signals are inherently weak, noisy, and susceptible to interference from the environment. VLSI readout circuits, fabricated using complementary metal–oxide–semiconductor (CMOS) technology, provide the essential interface for these sensors: they amplify, filter, condition, and digitize these feeble signals directly on-chip. This on-chip integration is critical; it minimizes parasitic capacitances and resistances that would otherwise swamp the tiny bio-signals, dramatically improves the signal-to-noise ratio (SNR), and enables the creation of compact, portable, and low-power devices. This report provides an exhaustive exploration of this synergistic integration. It begins with a detailed introduction to the core concepts and the pressing healthcare needs driving this technology. A thorough literature survey traces the historical evolution and theoretical foundations of both bio-MEMS sensors and VLSI readout architectures. The methodologies section offers an in-depth analysis of fabrication processes, circuit design principles, and the strategies for merging these two technologies. A presentation of key results demonstrates the remarkable capabilities of integrated systems, followed by a conclusion that summarizes the achievements, discusses persistent challenges, and outlines future directions toward intelligent, closed-loop therapeutic systems and the Internet of Medical Things (IoMT).