Following Ghanem's appointment as prime minister, Libya successfully sought re-entry into the international community and the lifting of sanctions.

Ghanem was seen as the main spokesman and architect of this rapprochement, which included paying $2.16 billion compensation in August 2003 to the families of the 270 people who died in the bombing, and renouncing weapons of mass destruction.

[8] He stirred controversy in the interview by repudiating Libya's responsibility both for the 1988 Lockerbie bombing and the 1984 murder of British WPC Yvonne Fletcher (who was shot and killed in April 1984 outside the Libyan Embassy in London).

It is unclear whether Shukri Ghanem's dismissal as prime minister in 2006 was a consequence of those controversial remarks he made two years earlier.

[12][6] Prior to his death, the interim Libyan government was preparing an Interpol arrest warrant against him, to investigate his mismanagement of oil production.

[19] On 1 May 2012, Reuters reported that Ghanem's associates at other OPEC countries, including former Iraqi Oil Minister Issam Chalabi, did not believe the official account of his death.

[20] In March 2019, The Independent reported that Ghanem was the go-between for many of the bribes paid to the Gaddafi regime by companies in the Western world, most notably Yara International.

Dutch prosecutors were simultaneously pursuing a case against a $700 million hedge fund operated by Ghanem's son-in-law, Ismael Abudher.

According to Dutch investigators, Abudher owned at least twelve British Virgin Islands shell companies and were using them to embezzle money from Libya's sovereign wealth fund, the Libyan Investment Authority.