He was re-elected as a member of the National Assembly in the 2008 general election for the seventh time, both from constituency NA-52 (Rawalpindi-III) and from constituency NA-53 (Rawalpindi-IV). Later, Khan vacated the NA-52 seat and retained NA-53.
Khan was appointed as the Federal Minister for Food, Agriculture and Livestock and Federal Minister for Communications in March 2008 in the government of Yousaf Raza Gillani, but his tenure was short-lived due to PML-N's decision to leave the Pakistan Peoples Party-led coalition government.
In September 2008, he was appointed as the Leader of the Opposition in the National Assembly after the resignation of Chaudhry Pervaiz Elahi. In October 2011, he became the first-ever chairperson of the Public Accounts Committee of the National Assembly (which was created to audit the accounts of the government) to present annual reports, but he resigned in November 2011 claiming that accountability was not possible under the Pakistan Peoples Party regime led by President Asif Ali Zardari and Prime Minister Gilani.
Nisar was appointed at position of 3 Ministries under Yousaf Raza Gillani, when he was the face of PML (N) in 2008 Pakistani general election and remained for a short period of 2 months(from 31 May 2008 - 14 March 2008) as the party was in alliance with Pakistan Peoples Party, and at that time Nisar openly blamed Pervez Musharraf and PML (Q) over weak Law and Order. He was assigned 3 ministries:-