The two north African countries have won nine of the 15 finals between them in the African equivalent of the UEFA Europa League.
Tunisian outfit CS Sfaxien lead the way with a record three titles, including back-to-back victories in 2007 and 2008, and they were drawn against Nkana FC from Zambia.
Sfaxien have already eliminated one Zambian club, defeating Green Buffaloes 4-2 on aggregate in a qualifier, and look set to reach the semi-finals.
Fellow Tunisians and twice trophy-holders Etoile Sahel will be favoured to eliminate Waleed Bakhet-inspired Al Hilal of Sudan despite patchy form en route to the knockout phase.
Bakhet scored twice last weekend in a 4-1 hammering of Nkana to top the scoring charts on six goals with Godwin Aguda from eliminated Enugu Rangers of Nigeria.
Gor Mahia of Kenya need to perform better away from Nairobi if they hope to overcome Renaissance Berkane of Morocco, whose stars include Togolese striker Kodjo Fo-Doh Laba.
Hopes of two Moroccan semi-finalists could be dashed by nine-time CAF title winners Zamalek of Egypt, who have already defeated Ittihad Tangier from the north African kingdom.
Zamalek are long overdue an African title having last succeeded 16 years ago when they lifted the CAF Super Cup.
Draws
Quarter-finals
Nkana FC (ZAM) v CS Sfaxien (TUN)
Etoile Sahel (TUN) v Al Hilal (SUD)
Hassania Agadir (MAR) v Zamalek (EGY)
Gor Mahia (KEN) v Renaissance Berkane (MAR)
First legs: April 7, second: April 14
Semi-finals
Nkana/Sfaxien v Gor/Berkane
Agadir/Zamalek v Etoile/Hilal
First legs: April 28, second: May 5
Final
Nkana/Sfaxien/Gor/Berkane v Agadir/Zamalek/Etoile/Hilal
First leg: May 19, second: May 26
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