Prof Mackay obtained her PhD in 1994 at the Louis Pasteur University in Strasbourg under the co-supervision of Dr Werner Lesslauer (Hoffmann La Roche, Basel Switzerland) and Prof Diane Mathis (now at the Joslin Institute Boston USA). In 1994, Prof Mackay joined BiogenIdec Inc. in Boston where she dissected the role of a TNF-like ligand lymphotoxin-alpha/beta in autoimmunity and cancer.

This work led to many patents and the development of two new treatments tested in the clinic. In 2000, Prof Mackay joined the Garvan Institute in Sydney as a Wellcome Trust senior research fellow and was awarded a NHMRC program grant. Prof Mackay's lab at Garvan discovered the role of a new molecule named BAFF as a key B cell survival factor essential for the maturation of B-lymphocytes but also playing a role in autoimmunity, and became one the leading group on BAFF research. In March 2006, Prof Mackay was appointed to Director of the Autoimmunity Research Unit and adjunct full Professor at the Faculty of Medicine, University of New South Wales and University of Sydney. Prof Mackay is a consultant for several biotech and pharmaceutical groups. From 2007-2009, she joined the National Director Board of the Australian Society of Medical Research (ASMR).

In 2008, she was the NSW representative for the NHMRC Association for Research Fellows (NARF). Prof Mackay is an associate editor and guest editor for several scientific journals. In March 2009, Prof Mackay became the 5th Chair of the Department of Immunology, Monash University, AMREP campus. In July 2009, belimumab, a therapeutic antibody neutralising BAFF has met the primary endpoints in a phase III clinical trial with lupus patients and run by GSK and Human Genome Sciences. This clinical outcome validated a decade of Prof Mackay's work on BAFF and autoimmunity.

In 2012, Prof Mackay received the Thomson Reuters Australia citation and innovation award; 2013 awarded NHMRC Best Research Project; 2014 received a trophy from the French Ministry of Foreign Affairs in Paris for outstanding contribution in education and research as an expatriate; and 2015 was elected as Council Member of the International Cytokine & Interferon Society. In September 2015, Prof Mackay was appointed the inaugural Head of the School of Biomedical Sciences at the University of Melbourne and in 2017 was elected as Fellow of the Australian Academy of Health and Medical Sciences.