The Saints lost their top scorer from the last four seasons to Liverpool prior to the World Cup, with the Merseyside-born star completing a dream switch to his boyhood club.
Graziano Pelle has since been snapped up to help fill the void, but manager Ronald Koeman also has his eye on Guidetti.
The Swedish international has long been dubbed as one of City’s best young players, but he has struggled to break into their first-team squad due to competition and injuries.
The 22-year-old starred during a loan stint at Feyenoord during 2011/12, netting 20 goals in just 23 games under the guidance of Koeman.
The Dutchman has since remained keen on the Scandinavian, and is now considering a swoop for his signature.
Guidetti spent the latter half of last season on loan at Stoke, and is thought to be available this summer.
Southampton could push for a temporary switch with a view to a permanent transfer at the end of the coming campaign.