Microcalorimeters play a critical role in biomedical and chemical research, such as dynamic monitoring of cellular metabolism, biomolecular interactions, and drug-receptor binding heat analysis, owing to their advantages of minimal sample requirements, rapid detection, and high precision. However, existing high-resolution microcalorimeters predominantly rely on micro-electro-mechanical systems processes, which involve complex photolithography, etching, and vacuum packaging techniques to fabricate microreactors and sensor arrays. These processes result in high costs and prolonged production cycles, limiting their adoption in low-cost, high-throughput scenarios. To address these challenges, this study presents an open-architecture microcalorimeter chip based on flexible printed circuit technology. The chip utilizes a flexible polyimide film substrate, integrates surface-mounted thermistors as temperaturesensing units, and combines an open reaction chamber design with differential signal processing circuitry. The device achieves a power resolution of 15.4 nW and a temperature resolution of 48.44 μK under ambient pressure. A thermal reaction monitoring system was developed to perform real-time thermal detection of water droplet evaporation processes. For a 0.4 μL droplet, the measured evaporation enthalpy was 960.9 mJ, deviating by only 1.91% from the theoretical value (979.63 mJ), validating the system′s high reliability and anti-interference capability. The proposed flexible microcalorimeter features simple fabrication, low cost, and scalable production, offering a cost-effective solution for fundamental studies in single-cell metabolic thermodynamics and nanomaterial heat capacity characterization. Furthermore, it demonstrates broad application potential in portable biochemical detection, high-throughput drug screening, and industrial process monitoring, with promising implications for advancing precision medicine, biopharmaceuticals, and green chemical technologies.