<p>Synthetic opioids are introduced as an addition to medicinal instruments for pain management. When misused, they present a unique burden of effective regulation and policing of cross-border flows, as illicitly synthesized opioids emerge as products purposefully designed to evade a government’s regulation and interdiction at the border. Since 2017, fentanyl has become a prominent issue in Sino–American relations, with the second Trump administration’s reference to fentanyl-related matters as a justification for levying additional tariffs on imports from China. The prevailing viewpoint appears to be that China does not have an illicit fentanyl challenge of its own. However, the current state of affairs in popular narratives may well have stemmed from a lack of presentation of China’s fentanyl/opioids governance. This article provides an overview of the evolution of fentanyl governance in China since its introduction for medical use in the early 1970s. Like the United States, China has been making efforts to police illicit production, trade, and consumption within its society, in addition to cooperation with the United States and other countries on narcotic control for over four decades. The article further discusses the structural issues that will continue to factor in dialogue and cooperation between the functional agencies of China and the United States on enhanced management of fentanyl and other synthetic opioids moving forward. Regardless of how the 2025 tariff discussions progress, there continues to be value in fostering exchange in scientific knowledge on opioids and evidence-based cooperation between China, the United States, and the rest of the world.</p>