In the field of sensing, the development of sensors with high sensitivity, accuracy, selectivity, sustainability, simplicity, and low cost remains a key focus. Over the past decades, optical and electrochemical sensors based on molecular imprinting techniques have garnered significant attention due to the above advantages. Molecular imprinting technology utilizes molecularly imprinted polymers (MIPs) to mimic the specific recognition capabilities of enzymes or antibodies for target molecules. Recently, MIP-based sensors rooting in signal amplification techniques have been employed to enhance molecular detection level and thequantitative ability for environmental pollutants, biomolecules, therapeutic compounds, bacteria, and viruses. The signal amplification techniques involved in MIP-based sensors mainly cover nucleic acid chain amplification, enzyme-catalyzed cascade, introduction of high-performance nanomaterials, and rapid chemical reactions. The amplified analytical signals are centered around electrochemical, fluorescence, colorimetric, and surface-enhanced Ramantechniques, which can effectively realize the determination of some low-abundance targets in biological samples. This review highlights the recent advancements of electrochemical/optical sensors based on molecular imprinting integrated with various signal amplification strategies and their dedication to the study of trace biomolecules. Finally, future research directions on developing multidimensional output signals of MIP-based sensors and introducing multiple signal amplification strategies are proposed.