Extracellular vesicles (EVs) have garnered tremendous attention for their role in facilitating intercellular communication by transporting biomolecules and chemical compounds to recipient cells. This has sparked interest in their potential as targeted delivery systems for therapeutic agents. Researchers are exploring ways to enhance these capabilities by engineering the composition of EVs to ensure they are taken up by specific subpopulations of recipient cells. For EVs to serve effectively as delivery vehicles for targeted therapies, it is crucial that they are internalized by the intended cells, allowing them to release their cargo. However, despite extensive research, the factors that regulate the entry of EVs and synthetic lipid nanoparticles (LNPs) into target cells, as well as the mechanisms that enable them to evade lysosomal degradation and release their contents, remain largely unclear. One challenge contributing to this knowledge gap is the difficulty in tracking the binding, internalization, and intracellular movement of these particles. To address this issue, significant efforts are being made to develop innovative techniques for monitoring and quantifying the internalization and intracellular dynamics of EVs and other nanoparticles. In this context, we will discuss the key factors to consider when designing such methods and review five innovative strategies for labeling, tracking, and quantifying the internalization of EVs and synthetic LNPs.