From 1988 he was employed in Konjic where he worked as clerk of town planning, construction and housing and communal services, market and catering inspector. From 1990 until 1992 he was Head of the Inspection.
In 1993, Nikšić joined to the Social Democratic Party of Bosnia and Herzegovina. Year later he became president of the SDP in Konjic. During the Bosnian War he served as assistant to the commander of the 7th Brigade for legal jobs and assistant to the commander of the 43rd Brigade for moral.
From 1995 until 1998 he was Vice President of the Executive Committee of the Municipality of Konjic, and from 1998 until 2000 he was Head of General Administration, Housing and Communal Services and Inspections. In 2000 he was named Deputy Mayor of Konjic, but he soon resigned since he became member of the House of Representatives of Bosnia and Herzegovina. From 2002 until 2006 he was vice president of the SDP clup in the parliament. In 2004 Nikšić became president of the SDP BiH in Herzegovina-Neretva Canton. In November 2006 he was president of the SDP parliamentary club. In January 2007 Nikšić become General Secretary of the SDP BiH.
In March 2011, after shorter political crisis in Bosnia and Herzegovina, he was named Prime Minister of the Federation of Bosnia and Herzegovina. Political crisis occurred after the elections when major parties were unable to have an agreement to form the new government.
Nikšić is married to Nadja and he has two children, daughter Najra and son Haris.