The Portugal international's arrival, reportedly worth more than €70 million, ranks among the biggest transfers in Serie A history and has strengthened the belief that Milan's recruitment strategy is gathering momentum under new head coach Ruben Amorim.
Italian reports claim Amorim recently met owner Gerry Cardinale, player transfer director Hendrik Almstadt and football intelligence director Bobby Gardiner in Lisbon as planning continues for the remainder of the transfer window.
Much of Milan's recruitment has centred on the Portuguese market, with Jorge Mendes' client network also featuring prominently among reported targets.
Benfica centre-back António Silva was identified as a leading defensive option, but negotiations have reportedly stalled after the Portuguese club demanded around €30 million for a player entering the final year of his contract.
That valuation has led AC Milan to cool their interest, at least for now, forcing the club to assess alternative options.
Lecce defender Tiago Gabriel has emerged as one of the leading domestic candidates, although reports suggest Lecce value the centre-back between €35 million and €40 million after previously attracting interest from the Rossoneri.
Milan are also monitoring opportunities abroad.
Manchester City defender John Stones has been linked as a possible market opportunity with his contract about to expire, while Manchester United centre-back Lisandro Martínez is another player Amorim knows well and is reportedly admired by the club.
Further changes could also arrive in midfield.
Sporting CP midfielder Morten Hjulmand remains a player appreciated by Amorim following his previous spell in Serie A with Lecce, while Barcelona midfielder Marc Casadó has also been proposed to Milan.
The futures of AC Milan goalkeeper Mike Maignan and AC Milan midfielder Adrien Rabiot are also uncertain following Massimiliano Allegri's departure, with both players said to have enjoyed close relationships with the former coach.
Meanwhile, AC Milan winger Rafael Leão's future continues to attract attention, although no formal offers have been reported. Amorim's arrival is viewed as a factor that could persuade the Portugal international to remain, while questions also persist over the long-term future of AC Milan winger Christian Pulisic.