During the first Benazir Bhutto government, Kanju for the first time became a part of the opposition headed by Nawaz Sharif. In the general elections of 1990 Kanju was for the third time elected Member of National Assembly for Lodhran, and at the behest of his friend and mentor Hamid Raza Gilani, joined the Nawaz Sharif cabinet as Pakistan's Foreign Minister (1990-1993). During this period in 1991 he changed Lodhran's status to a district, which was a tehsil of Multan District.
In the General Election of 1993 Kanju, who was perceived as a success of the Muslim League, lost his National Assembly seat for Lodhran district. Jang reported his failure was due to extensive travel made as Foreign Minister and absence from the constituency. During the period 1993-1996 Kanju spent most of his time in Lodran. He was again elected Member of National Assembly on Muslim League ticket. Once again he became part of Mohammad Nawaz Sharif's Cabinet, as Foreign Affair Minister, and served in this capacity until the Muslim League government was dissolved by the military coup of 1999. Siddique Kanju was the second person, after Zulfiqar Ali Bhutto, who served as Pakistan Foreign Minister for as long as six years in a civilian government.
When Mian Nawaz Sharif left the country, Siddique Kanju with his group of members joined the new faction of Muslim League headed by Chaudry Shujjat Hussain, former Interior Minister under Nawaz Sharif, and Mian Azhar who was a former Governor of Punjab.
During the local government elections of 2001 once again Kanju actively started campaign in his constituency. On 28 July when he was visiting a Counsellor shop in tehsil Kehrore Pakka he was shot by three or four assassins. Security high alert was declared in Islamabad and other cities. A former MPA, Mohammad Aslam Khan Joea and one of his party workers were also shot. The place where Kanju died was that where he gave his first speech as an incumbent in 1977 and started his career in politics.
Siddique Kanju died at the age of 49 years. His burial was attended by thousands of people, and was reported as the largest after the burial of President Zia-ul-haq. People from all walks of life condemned this act, and President Musharraf responded it by saying it was a big loss. Interior Minister Moin-u-din Haider and Governor Mian Mohammad Soomru took special notice and directed IG Punjab to take strict action.
Abdul Rehman Kanju, son of Siddique Kanju, later became the District Nazim of Lodhran. Two of assassins were arrested by the police later in 2002.