The Victorian Labor caucus will meet on Saturday to confirm the make-up of its cabinet after the resignation of MPs James Merlino, Martin Foley, Lisa Neville and Martin Pakula from their high-profile portfolios.
Current Agriculture and Regional Development Minister Mary-Anne Thomas will become health minister, while Corrections Minister Natalie Hutchins will pick up the education portfolio.
It is expected to be the Andrews government's final cabinet reshuffle before the November election, with new ministers likely to be sworn in early next week.
Mr Andrews confirmed five MPs would enter his latest cabinet, accounting for the four retiring ministers plus Labor stalwart Richard Wynne who has also stepped down after last year announcing he would call time on his political career at the election.
Senior Victorian Labor leadership will recommend to caucus that Transport Infrastructure Minister Jacinta Allan replace Mr Merlino as deputy premier.
That would go against Labor's convention to share the two top jobs between the Socialist Left and Right factions, given Mr Andrews and Ms Allan are both members of the former.
Treasurer Tim Pallas said he would lobby his colleagues from the Right to put factional politics aside and support Ms Allan.
"She will be a great demonstration ... of this government's renewal," he said.
Mr Andrews said there was flexibility in the arrangement under the Bracks and Brumby governments, referring to former deputy premier John Thwaites and his successor Rob Hulls.
If successful, the promotion would move Ms Allan closer to becoming Victoria's first female premier since Joan Kirner three decades ago.
But Mr Andrews insists he has the energy for another four years if re-elected in November, despite nearly becoming paralysed in a serious fall last year.
"I didn't get well to get out," the premier said.