Tunisian clubs Esperance and CS Sfaxien were placed in the same CAF Champions League group when the draw was made in Cairo on Tuesday.
Former Dutch star Ruud Krol will add spice to the derbies as he coached Sfaxien in 2013 before switching to Esperance.
Democratic Republic of Congo outfits TP Mazembe and Vita also clash at the mini-league stage of the premier African club football competition.
Esperance, Sfaxien, Algerians Entente Setif and Libyans Al-Ahly Benghazi are in a Group B composed exclusively of north African sides.
Group A comprises Mazembe, Vita, Sudanese Al-Hilal and Egyptians Zamalek, five-time winners of the competition.
Predicting likely semi-finalists is difficult this year in a shock-riddled competition, but Esperance, Sfaxien, Mazembe and Zamalek appear the strongest quartet.
Each side plays their three rivals home and away between mid May and late August with group winners and runners-up advancing to the semi-finals.
The winners of the two-leg final pocket $US1.5 million (1.1 million euros) and a place at the 2014 FIFA Club World Cup in Morocco during December.
Zamalek are the most successful of the eight qualifiers, although the last triumph of the Cairo White Knights in the competition was 12 years ago.
They eliminated Nigeriens Douanes, Angolans Kabuscorp and Zambians Nkana in qualifiers and veteran goalkeeper Abdel Wahed El-Sayed has not conceded a goal in six matches.
Mazembe have four titles and are back in the group stage after a shock early exit last year against South Africans Orlando Pirates.
Guided by France-born former Mali coach Patrice Carteron, the Ravens from mining city Lubumbashi had a mixed passage.
After easily overcoming Cameroonians Astres Douala, they needed an away goal to squeeze past Ivorians Sewe San Pedro.
Esperance have lifted the trophy twice, most recently in 2011, and boast the joint leading Champions League scorer this season in six-goal Haythem Jouini.
The Blood and Gold were far too good for Kenyans Gor Mahia and Malians Real Bamako and are among the title favourites.
Setif and Vita have been African champions once, but some of their players were not born when those triumphs occurred.
Vita won the 1973 title, when the competition was far less demanding, and Setif succeeded 15 years later under the former knockout-only format.
Setif share with Zamalek the distinction of not conceding a goal in this campaign as they eliminated Burkinabe ASFA Yennenga and Cameroonians Coton Sport.
Vita had the toughest passage of the eight qualifiers – overcoming Nigerians Kano Pillars, Zimbabweans Dynamos and South Africans Kaizer Chiefs.
Hilal have been Champions League runners-up twice and Sfaxien once while Benghazi are group debutants after shocking title-holders Al-Ahly of Egypt last month.
A: TP Mazembe (COD), Al-Hilal (SUD), Zamalek (EGY), Vita (COD)
B: Esperance (TUN), CS Sfaxien (TUN), Entente Setif (ALG), Al-Ahly Benghazi (LBA)