
Radja Nainggolan tiba di Piacenza Calcio pada akhir tahun 2005 pada usia 17 tahun, dari tim K.F.C. Germinal Beerschot. Ia berhasil tampil pada dua pertandingan Serie B untuk klub, selama dua musim terpisah. Nainggolan bermain dalam 38 pertandingan pada Serie B musim 2008-2009 untuk tim asal Emilia-Romagna tersebut, ia mencetak tiga gol yang akhirnya finis diurutan ke-10. Pada 27 Januari 2010 ia dipinjamkan ke Cagliari Calcio di Serie A, dengan opsi untuk membelinya secara permanen di akhir musim. Dia membuat debut liga pada tanggal 7 Februari, bermain dalam tujuh menit saat kekalahan tandang Cagliari 0-3 atas Inter Milan.
Pada 21 Juni 2010, Cagliari mengakuisisi Nainggolan secara permanen. Pada awal Oktober 2013, setelah tiga musim sebagai pilihan pertama yang diperdebatkan, ia memperpanjang kontrak hingga 2016. Namun, pada 7 Januari tahun berikutnya, Nainggolan dipinjamkan ke sesama klub Serie A, A.S. Roma sampai akhir musim dengan biaya € 3 juta, dengan opsi Roma membuat kesepakatan permanen pada musim panas berikutnya untuk harga € 6 juta. Nainggolan melakukan debut untuk tim barunya pada 9 Januari 2014, saat Roma meraih kemenangan kandang 1-0 atas U.C. Sampdoria pada ajang Coppa Italia musim 2013–2014, yang membuat Roma lolos ke perempat final.[15] Pada kompetisi yang sama, ia juga membantu menyingkirkan Juventus F.C. dengan bermain selama 90 menit penuh pada 12 hari kemudian. Nainggolan tampil pertama kali bersama tim nasional Belgia pada 29 Mei 2009, melawan Chili pada ajang Piala Kirin.
Nainggolan arrived at Piacenza Calcio 1919 in late 2005 at the age of 17, from local K.F.C. Germinal Beerschot. Still a junior he managed to appear in two Serie B games for the club, over the course of two separate seasons. Nainggolan played 38 matches in the 2008–09 campaign for the Emilia-Romagna side, scoring three goals for an eventual 10th-place finish. On 27 January 2010, Nainggolan was loaned to Cagliari Calcio in Serie A,[9] with the Sardinians having an option to buy the player permanently at the end of the season. He made his league debut on 7 February, playing seven minutes in a 0–3 away loss against Inter Milan. On 21 June 2010, Cagliari acquired Nainggolan on a permanent basis. In early October 2013, after three seasons as an undisputed first-choice,[11] he renewed his contract until 2016. However, on 7 January of the following year, Nainggolan was loaned to fellow league team A.S. Roma until the end of the campaign for a fee of €3 million, with an option to purchase 50% of his rights in the ensuing summer for €6 million.
Nainggolan made his debut for his new club on 9 January 2014, starting in a 1–0 home win over U.C. Sampdoria for the season's Coppa Italia which qualified to the quarter-finals. In the same competition, he also helped dispose of Juventus F.C. in said stage by playing the full 90 minutes 12 days later. On 22 February 2014, Nainggolan scored his first goal for the capital side, grabbing the 1–0 winner against Bologna F.C. 1909. His second, which arrived on 19 April against ACF Fiorentina (same result) ensured his team automatic qualification to the UEFA Champions League. Nainggolan signed a permanent deal with Roma in the 2015 off-season, for €9 million.