| Date: | 11–17 October |
| Edition: | 1st |
| Surface: | Clay |
| Location: | Ercolano, Italy |
| Champs: | Tallon Griekspoor |
| Champd: |  Marco Bortolotti /  Sergio Martos Gornés |
The 2021 Vesuvio Cup was a professional tennis tournament played on clay courts. It was the first edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Ercolano, Italy between 11 and 17 October 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Argentina | Federico Coria | 67 | 1 | |
| Italy | Marco Cecchinato | 82 | 2 | |
 France | Hugo Gaston | 112 | 3 | |
 Slovakia | ||||
| Tallon Griekspoor | 118 | 5 | ||
| Slovakia | Andrej Martin | 120 | 6 | |
| Spain | Bernabé Zapata Miralles | 122 | 7 | |
| Yannick Hanfmann | 125 | 8 |
The following players received wildcards into the singles main draw:
The following player received entry into the singles main draw using a protected ranking:
The following player received entry into the singles main draw as an alternate:
The following players received entry from the qualifying draw:
The following player received entry as a lucky loser:
See main article: 2021 Vesuvio Cup – Singles.
Alexander Ritschard 6–3, 6–2.See main article: 2021 Vesuvio Cup – Doubles.
Marco Bortolotti / Sergio Martos Gornés def. Dustin Brown / Andrea Vavassori 6–4, 3–6, [10–7].