The Seasiders reached the semi-finals of the competition last season, but were unable to book their place at Wembley.
Changes are expected for the visit of the League Two side on Tuesday night, through both rotation and necessity.
Interim head coach Richard Keogh will be without a number of players due to both injury and international call-ups.
Here’s our predicted XI and bench to take on Crewe:
1. Who will start for the Seasiders?
Blackpool take on Crewe Alexandra in the EFL Trophy. Photo: CameraSport - Lee Parker
2. Harry Tyrer
Harry Tyrer could make his Seasiders debut following his loan move from Everton last week. Photo: Blackpool FC
3. Odeluga Offiah
Odeluga Offiah could also make his first appearance in Tangerine after his Deadline Day move from Brighton. Photo: Blackpool FC
4. Matthew Pennington
Matthew Pennington has had a tough start and will be looking for a more positive display. Photo: CameraSport - Lee Parker
5. James Husband
James Husband has also struggled at times since being handed the armband at the start of the season. Photo: CameraSport - Lee Parker
6. Jordan Lawrence-Gabriel
Jordan Lawrence-Gabriel started in Blackpool's back three in Saturday's 2-2 draw with Wycombe Wanderers, but could return to a wing-back role on Tuesday night. Photo: CameraSport - Lee Parker