Since its establishment in 1967, the Association of Southeast Asian Nations (ASEAN) has continued to prove their consolidated and integrated model in political relations, economic development, and cultural values over 55 years. However, almost Southeast Asia countries have also faced the unpredictable impacts of transnational narcotics trafficking (TransNT), particularly synthetic drugs. The study uses regional and national reports as primary data combined the open-source intelligence (OSINT) as secondary resources to examine complicated situations in Southeast Asia. This article analysed the trend and pattern of drug trafficking among triangulated dots from the original countries via transit dots to the final destination countries, with some overlapped cases overlapped among those connections for reflecting the unpredictable movements of traffickers. Findings indicate that this region is still the predominant area for producing and trading synthetic drugs. The paper clarifies ASEAN’s milestones in building its cooperative mechanism to combat TransNT with specific initiatives. The study also demonstrates five main barriers in regional cooperation, including 1) conflicts in legal matters, 2) obstacles in capacity building, 3) challenges in regional trust, 4) limits in information exchange, and 5) unbalances in professional training. It must solve within the scope of regional cooperation, either ASEAN itself or their counterparts, including China, rather than national responses alone. This research also calls for further research in the next times before ASEAN moves forward as a community in 2025 and beyond with some specific recommendations.