Roll-Mecak attended high school at the Gheorghe Lazăr National College in Sibiu, in the Transylvania region. The school specializes in science education. She received her bachelor's degree in chemical engineering from Cooper Union in New York City, which operates on a full-tuition scholarship basis. During her undergraduate studies, she completed a summer internship at Mount Sinai School of Medicine, where she worked with Ernie Mehler and Harel Weinstein. Part of her inspiration to pursue structural biology came from a seminar on protein structure she attended at the New York Academy of Sciences as a student. She received her Bachelor of Engineering summa cum laude in 1996.