Breakthrough pain (BTP) is highly prevalent (59.2%) in chronic cancer patients and normally needs rescue treatments' with opioids when pain flares up. Transmucosal oral/nasal fentanyl formulations are commonly used in clinical practice. The different methods of release influence the pharmacokinetics and clinical properties of these formulations. The aim of this review was to assess and weigh these differences. Clinical trials comparing one transmucosal fentanyl with placebo or another active drug were included. We searched Medline for the last ten years and analyzed 13 studies, totaling 1447 patients. Clinical data on efficacy and safety were compared. In parallel, we report the differences in delivery systems, bioavailability, maximum plasma concentration (Cmax), plasma half-life, and time to reach Cmax (tmax). Considerable variability emerged between formulations. This suggests some considerations on the choice of the fentanyl formulation in the light of the BTP features in each clinical case.