MacTiernan studied at the University of Western Australia where she completed an arts degree and a law degree. She started her career with the federal government, in the area of Aboriginal employment and training. She was elected to the Perth City Council in 1988, where she remained until 1994. In 1993, she was elected as the member for the East Metropolitan region in the Western Australian Legislative Council. She was Minister for Planning and Infrastructure in the Western Australian government from 2001 to 2008. During that time she established the Public Transport Authority which helped to transform the planning and management of public transport, particularly in Perth. Her period in office saw the construction of many railway and road projects, including the building of the 70-kilometre-long Mandurah Line, the extensions of the Joondalup Line, Mitchell Freeway, and the Roe and Tonkin Highways, as well as the Kwinana Freeway/Forrest Highway extensions. In early 2010, she announced her plans to contest the Liberal-held federal seat of Canning, which included her state seat, and on 26 February 2010 resigned from the shadow ministry. She officially resigned from state parliament on 19 July 2010, two days after prime ministerJulia Gillard had announced the timetable for the 2010 federal election. Despite particularly strong results in areas which she had previously represented, MacTiernan came up short of victory, only garnering a 2.16 percent swing—three points short of what she needed to take the seat from Llberal incumbent Don Randall. She was elected as the mayor of the City of Vincent in October 2011. After Stephen Smith revealed that he was going to retire as member for the federal electorate of Perth at the 2013 federal election, MacTiernan announced her intention to contest the seat for the ALP, and the only other candidate for Labor pre-selection Matthew Keogh withdrew his nomination. At the election on 7 September, MacTiernan was successful in winning the seat despite a 1.5% swing against her. In July 2014 it was reported that a UMR "robo-poll" of 23 federal electorates, conducted for the National Tertiary Education Union, had found that MacTiernan was the second most popular federal MP, with an approval rating among her own constituents of +30. MacTiernan announced in February 2016 that she would not be contesting her seat at the 2016 federal election. She was succeeded by Labor's Tim Hammond. In August 2016 MacTiernan announced she would return to Western Australian state politics, and was placed as WA Labor's first candidate for the North Metropolitan electoral region. The landslide victory for WA Labor at the 2017 state election ensured her return to the Legislative Council. In 2019 it was reported that MacTiernan had been diagnosed with breast cancer, and had undergone surgery and chemotherapy.