Natural caffeine from decaffeination processes is widely used by pharmaceutical, cosmetic and soft-drink industries. Supercritical CO2 extraction (SFE−CO2) is extensively exploited industrially, and one of its most representative applications is the decaffeination process, which is a greener alternative to the use of organic solvents. Despite its advantages, extraction kinetics are rather slow near the CO2 critical point, meaning that improvements are highly sought after. The effect exerted by a combination of SFE−CO2 and ultrasound (US−SFE−CO2) has been investigated in this preliminary study, with the aim of improving mass transfer and selectivity in the extraction of caffeine from green coffee beans. This hybrid technology can considerably enhance the extraction efficiency and cut down process time. Further studies are in progress to demonstrate the complete decaffeination of green coffee beans of different types and origins.