Italy lost 1-0 in the first leg of their qualification play-off to Sweden and were then unable to turn things around at San Siro on Tuesday (AEDT), as it was held to a 0-0 draw.
The former Torino coach has been under pressure ever since Italy failed to top their qualification group, and its FIFA World Cup failure is seemingly the final straw.
It marks the first time Italy will not be at a World Cup since 1958 when, coincidentally, Sweden were the host nation.
Ventura stated at his post-match news conference that he not yet quit, but hinted that the match would be his last in charge.
When cornered by a reporter for Mediaset on Tuesday and asked whether he intends to quit, the 69-year-old simply replied by saying "yes".
Carlo Ancelotti has been tipped by many to become Ventura's replacement.