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Severe pain is a common and distressing symptom experienced by many patients, especially those with cancer. Morphine, a potent opioid painkiller, is widely prescribed for pain relief. Monitoring morphine levels is important for optimizing treatment outcomes, ensuring patient safety, and preventing adverse events. This study presents a novel wearable microfluidic device-coupled electrochemical sensor for the sensitive and selective determination of morphine in sweat. The device, fabricated using 3D printing (multi-jet modeling (MJM) technology), incorporates a pumpless microfluidic system and a high-performance electrochemical sensor. An experimental design methodology was employed to optimize factors influencing sensor performance, thereby enhancing the sensor's selectivity and sensitivity. The sensor, based on a molecularly imprinted polymer (MIP) integrated with lanthanum metal-organic framework (MOF) and poly(amidoamine) dendrimer (PAMAM), exhibits excellent sensitivity with a detection limit of 0.0092 ng mL−1 and a wide linear range (0.04-0.10 ng mL−1 and 0.10-1.00 ng mL−1). The microfluidic device demonstrates a rapid response time, high sampling efficiency, and requires minimal sweat volume. Successful morphine determination in artificial and human sweat samples demonstrates the effective integration of the wearable microfluidic platform with the electrochemical sensing system. By combining wearable technology, microfluidics, and electrochemical sensing within a single device, the proposed system offers a promising strategy for non-invasive sweat-based morphine analysis and establishes a basis for further development toward broader real-world applications.