Leeds Rhinos' clash against Castleford Tigers at Headingley and St Helens' trip to Hull KR are the only two all-Super League ties in the fourth round of the Tetley's Challenge Cup.
The Tigers' only league victory came this season against local rivals Leeds while Saints suffered a 22-14 defeat to the Rovers in Sunday's game at New Craven Park.
Holders Warrington, who have won three of the last four finals, will be the favourites to win at Keighley Cougars while Wigan Warriors welcome Leigh Centurions to the DW Stadium.
London Broncos entertain Featherstone on home soil while the Wakefield Wildcats are also down south as they travel down the M1 to do battle with the Hemel Stags.
Hull FC, who have been eliminated at the first hurdle in three of the past four seasons, will be confident of seeing off the North Wales Crusaders at the KC stadium.
Catalan Dragons are back in England as they have been paired with the Hunslet Hawks while the other French team in the draw are also in Yorkshire as York City Knights host Toulouse.
Bradford Bulls make the trip across the M62 to take on the Rochdale Hornets while the Huddersfield Giants have the short trip to Batley on their fixture list later this month.
Widnes Vikings are at home to Doncaster while Super League strugglers Salford City Reds take on the brand new Gloucestershire All Golds, who are currently in their first-ever season of rugby league.
Warrington's long-serving stand-off Lee Briers, who kicked six goals in last year's 44-18 fourth-round victory over the Cougars, admits that experience will stand the holders in good stead.
"It was tough last year and it will be tough again," he said. "They gave it their all, which is what you expect.
"Last year we tried to tell the players what to expect about the changing rooms being tiny and the pitch and slope. We went in a bit blind but this year we're prepared.
"It's a classical old rugby league ground, the crowd is on top of you. It's one of the brilliant things about rugby league.
"Sometimes in Super League you get spoiled with brand new stadiums and massive changing rooms with five toilets and 12 showers. Sometimes you need a reality check."
Which team had the most impressive win from Super League round eleven?