Plastic pollution in the natural environment poses a growing threat to ecosystems and human health, prompting urgent needs for monitoring, prevention and clean-up measures, and new policies. To effectively prioritize resource allocation and mitigation strategies, it is key to identify and define plastic hotspots. UNEP’s draft global agreement on plastic pollution mandates prioritizing hotspots, suggesting a potential need for a defined term. Yet, the delineation of hotspots varies considerably across plastic pollution studies, and a definition is often lacking or inconsistent without a clear purpose and boundaries of the term. In this paper, we applied four common hotspot definitions to plastic pollution datasets ranging from urban areas to a global scale. Our findings reveal that these hotspot definitions encompass between 0.8% to 93.3% of the total plastic pollution, covering <0.1% to 50.3% of the total locations. Given this wide range of results and the possibility of temporal inconsistency in hotspots, we emphasize the need for fit-for-purpose criteria and a unified approach to defining plastic hotspots. Therefore, we designed a step-wise framework to define hotspots by determining the purpose, units, spatial scale, temporal scale, and threshold values. Incorporating these steps in research and policymaking yields a harmonized definition of hotspots, facilitating the development of effective plastic pollution prevention and reduction measures.