She also appeared in American director Mark L. Feinsod's first film, Love And Lung Cancer. Alongside her television work she has appeared in the films Gypsy Woman and One Last Chance. 2008-9 saw McIntosh starring in several new films including Salvage, Spring 1941 (with costar Joseph Fiennes) and the award-winning Be All and End All.
McIntosh is probably best known for her portrayals of Beryl Stapleton in the 2002 BBC version of The Hound of the Baskervilles, and of Fuchsia in the 2000 BBC and WGBH Boston production of Gormenghast, a lavish miniseries based on the first two books of the trilogy by Mervyn Peake. She also played the title role in Lady Audley's Secreat.
She appeared in the first British Sky Broadcasting-produced "Doc Martin" prequel (in which the Martin Clunes character was named Bamford, rather than his later moniker of Ellingham), as a lonely villager with an asthmatic son, to whom Martin is attracted.
In 2004, McIntosh starred in Bodies, a medical drama produced by BBC Three and based on the book Bodies by Jed Mercurio. She has also appeared in several other television dramas, including Psychos, Ghost Squad, Marple, Murder City, Bodies-2 and Low Winter Sun. It was during the production of Psychos that she met her cameraman husband Xandy Sahla from whom she was divorced in 2009. She also recorded an episode of Law & Order: UK.
In May 2010, McIntosh appeared in two episodes of the 2010 series of Doctor Who beside new Doctor played by Matt Smith. She plays two Silurian sisters who have been disturbed under the earth, one captured by humans and the other demanding vengeance. In October 2010, she starred alongside former Doctor Who star, David Tennant, in Single Father, a BBC drama. She portrayed the part of Anna, the sister of the dead wife of Tennant's character (Dave).
McIntosh returned as a new Silurian character, Madame Vastra, in the Doctor Who Series 6 mid-series finale episode "A Good Man Goes to War", which aired in the UK on 4 June 2011. The character is a sword-wielding, human-eating late Victorian crime fighter, and an old friend of The Doctor.
McIntosh appeared in the BBC One series Case Histories as Joanna Hunter which aired in June 2011. She also starred in Season 2 of the BBC Three drama, Lip Service, as a love interest of one of the main characters, Sadie.
McIntosh returned once again to Doctor Who in the 2012 Christmas special, and in the episodes The Crimson Horror and The Name of the Doctor. In all of these S7 episodes she reprises her role as as the Madame Vastra, who along with her wife Jenny Flint and Strax, a former Sontarian nurse, form an investigating team. While there is a suggestive chemistry between Vastra and her chambermaid Jenny in "A Good Man Goes to War" the later episodes explicitly mention that Vastra and Jenny are married.