Medunjanin was born in Sarajevo, SFR Yugoslavia, present-day Bosnia and Herzegovina. After the outbreak of Bosnian War in 1992, he moved to the Netherlands at the age of seven with his mother and sister, whilst his father was unable to leave, later losing his life. Due to living in the latter country, he possesses dual citizenship, Bosnian and Dutch.
Medunjanin made his Eredivisie debut on 20 February 2005, with AZ. During his three-year spell, however, opportunities were scarce.
For the 2006–07 season, he was loaned to Sparta Rotterdam, being essential as the modest club finished 13th by scoring seven league goals.
After another unassuming campaign in Alkmaar, Medunjanin was acquired by Spain's Real Valladolid in August 2008, being relatively used in his first year (mainly as a substitute).
In 2009–10, Medunjanin netted all of his five La Liga goals as a late substitute. In January 2010, he and other teammates were fined €6,000 for breaching club discipline by "engaging in untimely nocturnal activities", and the team was also eventually relegated.
In June 2010, Medunjanin signed a four-year contract with Maccabi Tel Aviv in Israel for €1.8 million. On 15 July he made his official debut for his new team, in a UEFA Europa League second qualifying round against Mogren, and scored in a 2–0 home win.
On 31 August 2012, Medunjanin signed with Turkish side Gaziantepspor on loan from Maccabi. The move was made permanent before the start of the following season, on a three-year deal.
On 12 August 2014, after a successful medical, free agent Medunjanin joined Deportivo La Coruña. On 29 January 2016, having been deemed surplus to requirements by new manager Víctor Sánchez, he terminated his contract, and agreed to a one-and-a-half-year deal with his former club Maccabi Tel Aviv two days later.
Medunjanin helped Maccabi qualify to the Europa League group stage in his second season.
On 31 January 2017, Major League Soccer club Philadelphia Union signed Medunjanin to a two-year deal with an option for a third. He made his debut in the season opener, in a 0–0 away draw against the Vancouver Whitecaps.
Medunjanin scored his first goal for his new team on 14 May 2017, contributing to a 4–0 success at D.C. United.
Medunjanin was part of the Netherlands under-21 team that won the 2006 tournament of the UEFA European Championship. He was also called by coach Foppe de Haan for his squad in the 2007 tournament, held in the Netherlands; the nation went on to retain its title by beating Serbia 4–1 in the final, and in the process qualify for the 2008 Olympic Games in Beijing.
In a 2009 interview, Medunjanin expressed strong desire to play for his native Bosnia and Herzegovina, as new FIFA rules would allow. In August of the same year, his paperwork for change of footballing citizenship was submitted to FIFA and, on 31 October 2009, national coach Miroslav Blažević invited the player for the 2010 FIFA World Cup playoff games against Portugal. He made his debut – as a starter – in the decisive second leg, a 0–1 loss in Zenica (0–2 on aggregate).
Medunjanin scored his first international goal on 17 November 2010, in a friendly against Slovakia. In the UEFA Euro 2012 qualifying campaign, he contributed with three goals against Albania (2–0, home), Belarus (2–0, away) and Luxembourg (5–0, home), helping Bosnia to the second place in their group and to qualify for play-offs.
On 2 June 2014, Medunjanin was named in the squad for 2014 FIFA World Cup. He made his debut in the tournament 14 days later, playing the last 16 minutes of a 1–2 group stage loss to Argentina.
On 13 October 2015, Medunjanin scored a crucial brace against Cyprus to help Bosnia and Herzegovina reach the Euro 2016 play-offs after the 3–2 away win. In 2016, he captained the nation during the Kirin Cup winning campaign.As of match played 17 September 2017.
As of match played 10 October 2016.
As of 6 September 2016
(Bosnia and Herzegovina score listed first, score column indicates score after each Medunjanin goal)
UEFA European Under-21 Championship: 2006, 2007