Extracellular vesicles (EVs) have been hypothesized to incorporate a variety of crucial roles ranging from intercellular communication to tumor pathogenesis to cancer immunotherapy capabilities. Traditional EV isolation and characterization techniques cannot accurately and with specificity isolate subgroups of EVs, such as tumor-derived extracellular vesicles (TEVs) and immune-cell derived EVs, and are plagued with burdensome steps. To address these pivotal issues, multiplex microfluidic EV isolation/characterization and on-chip EV engineering may be imperative towards developing the next-generation EV-based immunotherapeutics. Henceforth, our aim is to expound the state of the art in EV isolation/characterization techniques and their limitations. Additionally, we seek to elucidate current work on total analytical system based technologies for simultaneous isolation and characterization and to summarize the immunogenic capabilities of EV subgroups, both innate and adaptive. In this review, we discuss recent state-of-art microfluidic/micro-nanotechnology based EV screening methods and EV engineering methods towards therapeutic use of EVs in immune-oncology. By venturing in this field of EV screening and immunotherapies, it is envisioned that transition into clinical settings can become less convoluted for clinicians.