Naturally occurring lipid-enveloped nanoparticles, coined extracellular vesicles (EVs), bear exponential promise as functional therapeutic delivery vehicles. Recent studies have evidenced that the RNA cargo (particularly microRNAs; miRNAs) of EVs participates in altering recipient cell function, which has led researchers to investigate mechanisms to engineer/modify EVs miRNA cargo for mediation and functional delivery by means of regulating the gene expression of target cells. Here, we describe selected experimental techniques that have been used to investigate the dynamics and efficiency of miRNA loading into EVs and their subsequent capacity to deliver highly specialized cargo to targeted recipient cells. Notably, following the determination of identifying candidate miRNAs, we selected both “passive” and “active” loading measures to modify the basal miRNA cargo level found within the EVs. We intend to provide a comprehensive overview highlighting both the advantages and limitations of the specified methodical practices, as detailed in the outcome of a specified workflow on the generation of miRNA-modified EVs for downstream assessment using both quantitative and qualitative techniques to determine loading (EVs) and delivery (target cells) efficiencies. This chapter focuses on describing the methods and protocols for a subset of exogenous and endogenous strategies currently used for the targeted loading of miRNAs into EVs. Additionally, approaches used for determining their efficiencies and the mechanisms of targeted delivery of the proposed miRNAs into recipient cells will be discussed in detail.