Winless Samp sit bottom of Italy's top tier following defeat to Roma on Monday, and must recover quickly if they are to secure a last-16 encounter with Fiorentina, who await the winners of their second round tie.
Match preview
Since Sampdoria progressed to the Coppa Italia's second round with an unconvincing 1-0 win over Reggina back in August - a result earned by Abdelhamid Sabiri's second-half strike from the penalty spot - the Ligurian club have yet to taste success again.
The 1994 cup winners are experiencing an awful run of form in Serie A this season; continuing a dismal 2022 at Stadio Luigi Ferraris: last term they faced a fight to stay up, as Marassi co-tenants Genoa instead dropped out of the top flight.
If Samp are to avoid following their old rivals down to Serie B, recently-hired coach Dejan Stankovic will have to exact quite a turnaround, as his new club have lost seven of their league games to date and drawn the other three.
Their latest reverse came at home to Roma earlier this week, when they succumbed to Lorenzo Pellegrini's early penalty, and as a result, they remain rock-bottom of the standings.
Now enduring the club's worst run for 16 years, Stankovic's side is an ageing one - the Serbian coach inherited Serie A's oldest squad from predecessor Marco Giampaolo - and the challenge of reviving the Blucerchiati represents a major ask.
Perhaps the breathing space offered by cup football will alleviate some pressure on the four-time Coppa winners, and they now aim to at least match last year's run, in which they reached the third round before being eliminated by Juventus.
By contrast with their hosts, Ascoli have never won Italy's premier cup competition, and they have spent all but 16 years of their existence outside Serie A; with the club's last taste of the top flight ending some 15 years ago.
The Bianconeri came out on top in their first round trip to Stadio Pier Luigi Penzo in the summer, as they beat freshly-demoted Venezia 3-2 despite almost throwing the game away.
Leading by two goals heading into the final five minutes, Cristian Bucchi's side conceded twice in rapid succession, before a dramatic finale concluded with Anthony Fontana's stoppage-time winner for the much-relieved visitors.
The club's top goalscorer in 2004-05, Bucchi returned to Ascoli in June and has since led his new charges to three wins, three draws and three losses in Serie B, as they aim to improve on a failure to gain promotion last term.
Still very much within touching distance of the playoff spots, they can now take a free hit at struggling Sampdoria; seeking to set up a glamour tie in Tuscany after the World Cup break.
Sampdoria Coppa Italia form:
W
Sampdoria form (all competitions):
L
L
L
L
D
L
Ascoli Coppa Italia form:
W
Ascoli form (all competitions):
D
L
L
D
L
W
Team News
Ahead of Dejan Stankovic's first match at Marassi, Sampdoria were forced into a defensive reshuffle for Monday's loss to Roma, as Colombian centre-back Jeison Murillo sustained a hamstring injury which could keep him sidelined until the end of next month.
Alex Ferrari and Omar Colley may therefore be retained at the heart of the hosts' back four, though Bruno Amione presents an alternative should Stankovic rotate his resources prior to the upcoming clash with relegation rivals Cremonese.
Harry Winks recently returned to full training, but is not set to make his delayed Samp debut just yet, so Ronaldo Vieira competes with Tomas Rincon and Gonzalo Villar for a place in central midfield; veteran striker Fabio Quagliarella could feature up front.
Meanwhile, Ascoli saw Cedric Gondo sent off in the dying moments of their 2-0 success at Bari on Saturday, but his suspension only applies to next week's game against Cagliari. The Ivorian may therefore start, joining the experienced Federico Dionisi in a front pairing.
After scoring at the weekend, Croatian defender Lorenco Simic should line up at the back, having begun his Calcio career with Sampdoria back in 2017 - he never made a first-team appearance for the club.
Sampdoria possible starting lineup:
Audero; Conti, Amione, Colley, Murru; Vieira, Villar; Gabbiadini, Sabiri, Djuricic; Quagliarella
Ascoli possible starting lineup:
Guarna; Simic, Botteghin, Bellusci; Donati, Caligara, Giovane, Eramo, Falasco; Gondo, Dionisi