Multiscale Boiling is a European Space Agency funded experiment performed on-board the International Space Station (ISS) between 2019 and 2021 with as goal studying the basic physics of the boiling process. This paper focuses on the operational aspects and challenges of the Multiscale Boiling experiment, from its preparation to the execution on-board of the ISS and the lessons learnt. Multiscale Boiling implements a multi-scale approach, and includes the application of two external forces (electrical field and shear flow). In combination with the microgravity environment, the Multiscale Boiling experimental setup allows studying the basic physical aspects of the boiling process and allows the observation of effects that are too fast and too faint to be measured under normal gravity conditions. The process of boiling heat transfer depends on the environmental conditions. The nature of the experiment and the large number of experiment parameters result in a complex setup which requires careful monitoring and continuous real-time control by the ground operator, preventing a fully automated approach for the science runs. The Multiscale Boiling experiment was operationally challenging, as the conduct and result of the experiment was mainly relying on the expertise of the ground operator. Despite the challenges encountered during the mission, including several hardware anomalies, data of unprecedented quality could be obtained and the overall mission was considered as a success. The achievement of mission success was the result of the close collaboration between the different instances involved, being the international and multidisciplinary Science Team, the European Space Agency (ESA), the payload developer and the payload operations team.