In 1922 Karamichailova graduated as a PhD in Physics and Mathematics. She wrote her thesis, entitled "About Electric Figures on Different Materials, Especially On Crystals" under the direction of Karl Przibram. Karamichailova continued her work at the Institute for Radium Studies afterwards, becoming particularly interested in radioluminescence. She cooperated with Marietta Blau in the study of polonium, and later researched methods for neutron bombardment of thorium. Karamichailova simultaneously attended courses in electronic and radio engineering at the Vienna Polytechnic. In the autumn of 1923 she returned briefly to Bulgaria and worked as a "guest fellow" at the Physics Institute of Sofia University. Soon Karamichailova went back to Vienna and began her work on the transmutation of light elements under alpha radiation at the Institute of Radium Studies. In 1931, Karamichailova and Marietta Blau observed a specific type of previously unknown radiation emitted from polonium, which would later be confirmed by James Chadwick as neutron radiation, leading to his discovery of neutrons.
In 1933 the position of "research assistant", under which she worked in Vienna, was terminated. Karamichailova had to continue her research without tuition until 1935, when she obtained a 3-year Alfred Yarrow Research Fellowship from Girton College, Cambridge. She was subsequently employed at the Cavendish Laboratory. In December 1937, she applied for a position as a docent in Experimental Physics at Sofia University. Karamichailova managed to extend her scholarship by 10 months, and finally returned to Bulgaria in 1939, where she was appointed as a docent of Experimental Atomistics with Radioactivity at SU. She set up an atomic physics course, introducing the latest knowledge from her studies in Austria and England and some of her equipment. The outbreak of World War II halted any further expansion of nuclear research activities.
Her studies now involved cosmic rays as well. Karamichailova used photographic plates to continue her work in this field, which she had collaborated on with Marietta Blau. She attempted to continue the study of multiple ionization, but this was impossible without the sophisticated equipment she had access to while in England. When Karamichailova began her work in Sofia in 1940, she only had a microscope and a dark room.