In South Carolina (SC), the ORS team facilitated a cross-sector collaboration to ameliorate a drug disposal issue and ultimately, reduce the chances of overdose. At the end of the school year, school nurses in the state attempted to return unused prescriptions to parents and/or guardians; however, not all medications were picked up by families. School nurses are instructed not to transport medications off-site to a drug dropbox due to liability constraints, therefore, the appropriate solution for safe disposal was left unclear. To assist these schools, the SC Public Health Analyst (PHA) introduced the health department school nurse liaison to the prescription drug monitoring program director. The director connected the liaison with a resource to provide disposal bags and buckets to school nurses at a statewide conference. After exploring approaches used in different school districts and recommendations from state law enforcement with the SC Drug Intelligence Officer (DIO), the stakeholders also suggested that school resource officers could transport and dispose of the medications, similar to confiscated substances from other incidents. Through the PHA’s role as a connector between multiple parties and the DIO’s law enforcement expertise, the SC ORS team contributed to the clarification of best practices and a solution to prescription drug disposal from schools.