Bos worked as a human resource manager for Royal Dutch Shell from August 1988 until May 1998 in Pernis from August 1988 until September 1989 in Rotterdam from September 1989 until July 1991 in Bucharest, Romania from July 1991 until April 1993 in Hong Kong from April 1993 until November 1995 and in London, England from November 1995 until May 1998.

After the election of 2002 Bos returned as a Member of the House of Representatives, taking office on 23 May 2002 serving again as a frontbencher and spokesperson for Finances.

The following cabinet formation of 2006 resulted in a coalition agreement between the Labour Party, the Christian Democratic Appeal (CDA) and the Christian Union (CU) which formed the Cabinet Balkenende IV with Bos appointed as Deputy Prime Minister and Minister of Finance, taking office on 22 February 2007.

The Cabinet Balkenende IV fell on 20 February 2010 after tensions in the coalition over the extension of the Dutch involvement in the Task Force Uruzgan of the International Security Assistance Force (ISAF) in Afghanistan and continued to serve in a demissionary capacity until the Labour Party cabinets members resigned on 23 February 2010.

On 12 March 2010 Bos unexpectedly announced his retirement from national politics and that he wouldn't stand for the election of 2010 and approached Job Cohen as his successor.

In September 2018 Bos was appointed as chairman of the board of directors of the Netherlands Investment Agency, taking office on 1 October 2018.

He campaigned together with Rick van der Ploeg and Willem Vermeend as "the Polderboys" and gave lectures in economics at universities.

In the January 2003 election, Bos entered a head-to-head race with incumbent Prime Minister and leader of the Christian Democratic CDA, Jan Peter Balkenende.

[3] He spent considerable time reforming the PvdA's internal organisation and public image, together with the party's chairman Ruud Koole.

Although still enjoying large public support, criticism about his "style over substance" approach to politics was voiced in this period.

Some considered pension reforms proposed by him to embattle the consequences of an aging population as a reason for this decline in popularity.

[5] Bos lost nine seats in the elections, which saw large gains for the main rival of Labour on the left side of the political spectrum, the more radical Socialist Party.

[citation needed] As part of the leadership of the PvdA he revoked his confidence in fellow party member Ella Vogelaar as Minister of Integration and Housing.

Wouter and Barbara Bos have two daughters, Iris (5 February 2004) and Jula (3 January 2006) and a son Joppe (18 April 2009).