Telkes joined the Cleveland Clinic Foundation as a biophysicist. She worked alongside Dr. George Crile, Sr. on projects focusing on energy production in living organisms. Her research delved into the mysteries of life processes and how they converted energy, laying the foundation for her understanding of solar power.

Her efforts were specifically focused on measuring the energy production of living things, an area of research that was rather novel at the time. This experience gave her a new perspective on the potential for creating alternative forms of energy for human use.

While working at the Cleveland Clinic, she began considering the potential of harnessing solar energy. This interest was likely fueled by her understanding of energy conversion processes and her desire to find alternative energy sources.

She left the Cleveland Clinic to pursue her research interests in solar energy. In these years, she laid the conceptual groundwork for her later solar energy innovations.