The e-commerce sector has recently undergone considerable growth, causing various challenges related to last mile logistics and the accessibility of pick-up points (PUPs). In general, they enable the mitigation of certain crucial challenges facing the logistics sector, such as delivery fails and returns. The purpose of this article is to examine an example of a network of PUPs in Southern Europe, despite the fact that there are noteworthy examples from Northern Europe in the literature. The proposed methodology involves the analysis of the accessibility of PUPs, taking into account the 5-min isochrone, as well as the characterization of the activities that host them. The article uses as case study the network of pick-up points of the main e-commerce operator in Italy, in a medium-sized city in Sicily (<60,000 inhabitants) such as Acireale. According to the results, there is a reasonable distribution of pick-up points in the central areas that are easily accessible on foot, but there is a poor distribution and, for the most part, a need of using private vehicles in the suburbs. It is worth mentioning that the inhomogeneity of distribution is related to geographical reasons. The work lays the groundwork for further research; the formulation of resilient strategies and actions to be carried out by logistics companies, ideas concerning the optimization of deliveries, and concurrently, the attention given to accessibility aspects related to the last mile delivery by public administrators and planners.