<p>Prescription drug collection boxes have been deployed in many communities to collect unused prescription opioids and other medications to prevent misuse. However, their current ad hoc placement leaves some communities without nearby disposal options. This paper addresses this issue by exploring how to evaluate the performance of a network of prescription collection boxes and how to locate new collection boxes. To do so, we introduce performance measures based on the set cover problem to identify areas lacking access to prescription collection boxes, termed “deserts.” We then formulate the Collection Box Location Problem, an integer programming model based on the maximal covering with mandatory closeness problem, to strategically identify sites for new prescription collection boxes. We present practical model variants that incorporate restrictions on placing boxes only at non-law enforcement facilities, relocation of existing boxes under a budget constraint, and penalties for leaving regions without nearby access. A case study using data from Wisconsin illustrates the applicability of our methodology.</p>