A trip to Dublin follows on a Friday night to face Ireland on 6 March.
Ireland coach Andy Farrell only named two Welsh players in his British and Irish Lions squad for the successful series win in Australia.
Ospreys flanker Jac Morgan appeared in the series as a replacement in two tests, while Gloucester scrum-half Tomos Williams was injured before the series began.
Tandy’s side finish the campaign against Italy in Cardiff eight days later with the Azzurri aiming for a third successive win against Wales.
Italy have also won the past two matches at Principality Stadium and celebrated a statement victory against Australia in November 2025.
“It is true as a team we might have had some good results in the past couple of years,” said Italy coach Gonzalo Quesada.
“I know that the crisis that is in Wales and the situations with the clubs, but I also know how much pride they will put in this Six Nations and want to have a good performance with the national team.
“They know if Wales perform and has good results, it will be such a help with the transition they are going through now.”
Quesada also points to the difference in facilities between Italy and the other five nations involved.
“We know they have incredible facilities in Wales and all the conditions to prepare with,” said the former Argentina international.
“We are the only federation that do not have our own rugby training centre.
“It is not excuses, just facts and we do not mention it internally. We want to compete against Wales, as we want to compete against all the other sides.”