As the curtain closes on their top-flight stay, Samp arrive in Italy's second city on an eight-game winless run, while their hosts have won just one of their last four league matches to slip down the standings.
Defeat in the fifth and final Derby della Madonnina of the season saw Milan eliminated from the Champions League when just one step away from next month's final in Istanbul, as Inter again proved too good for their Rossoneri rivals.
Rarely threatening to mount a memorable fightback, the seven-time European champions followed last week's 2-0 loss with a one-goal reverse on Tuesday evening, and they have now lost their last four games against the Nerazzurri without scoring a single goal.
Such a setback sums up the climax to their 2022-23 campaign: handing over the Scudetto to Napoli without making much of a title defence, Stefano Pioli's side have won just three of their last 11 league matches following a humbling defeat to Spezia last Saturday.
With an injury-afflicted lineup at Stadio Picco, Milan came up short against the Serie A strugglers after conceding twice in the last 20 minutes, and considering points accrued since the start of March they would rank only 12th in the standings.
All of which leaves them four points adrift of Italy's top four with just three games left to play - two of which are against Juventus and a Verona side scrapping desperately for survival.