[1] Her father, John McLoone, built a hydroelectric scheme on the Oweneda river, which was close to O'Neill's house, providing the family with free electricity.

[4] She studied electronic engineering at Queen's University Belfast, and was sponsored by a local company to work on data security.

Her first interaction with entrepreneurship was during her doctoral training, when her PhD project on high speed Advanced Encryption Standard (AES) was successfully commercialised by an American semiconductor company for use in set-top boxes.

[5][13] She worked on security systems to protect users from cyber threats, and was made Head of the Cryptography Research Team.

[15][16] She worked on quantum dot cellular automata circuit design techniques, which are being considered as alternates to CMOS and have lower power dissipation.

[15] She also developed PicoPUF , a physical unclonable function (PUF) device that contained a semiconductor IP core to provide authentication for microchips, which was awarded the INVENT2015 prize.

[21][22] In 2017 she was made Director of the United Kingdom Research Institute in Secure Hardware and Embedded Systems, a £5 million centre in Belfast.

[3] In 2018 O'Neill was named the Principal Investigator of the Centre for Secure Information Technologies (CSIT) in the Northern Ireland Science Park.

[28] In August 2019 O'Neill was appointed acting director of ECIT, the Institute of Electronics, Communications and Information Technology at Queen's University Belfast.