Hot4cryo aims to attract and maintain a prominent researcher (ERA Chair) together with a high-quality supporting team to advance multidisciplinary research in the National Hellenic Research Foundation (NHRF) by founding the high-resolution electron cryo-microscopy Unit for Excellence, i.e., CryoUNITe, unique in Greece, the Balkans, and Southeast Europe. While cryo-EM technology is transforming international research in exciting, multiple directions, substantial disparity exists in its possession across European countries and is absent in the complete Southeast Europe. This hampers innovations in biomolecular and materials structure research and development and limits progress of EU Missions Cancer, Soil, and Green Deal, which align to the research directions of NHRF and the prospective ERA Chair Holder. Hot4cryo plans to address this issue, aims to eliminate this disparity, and envisions to urgently transmit the “resolution revolution” to Greece and the wider region, emerging as a cultural hub for seeding Horizon Europe’s strategic plan across players and the society. CryoUNITe will be embedded in NHRF, enhancing institutional structural transformations. Hot4cryo will bring high-end cryo-EM knowledge for a wide range of systems in alignment with ERA priorities. The modern technology and innovation potential involved will undoubtedly progress digital transformation within NHRF, improve research cohesion across all involved partners, and foster fundamental and applied research opportunities of outstanding quality. As a result of this action, hot4cryo will produce a Unit of Excellence, improve direct access to excellence for partners and collaborators and strengthen the interactions between science and society. Ultimately, hot4cryo will contribute to reverting the current brain drain to “brain gain” while promoting brain circulation within the EU, positively affecting local and regional economies.