The state government will invest between $510 million and $560 million into the medical centre for up to 108 additional inpatient beds and an extra 7500 surgeries will be performed annually.
"This is great for jobs, great for healthcare and absolutely terrific when it comes to more services close to home," Premier Daniel Andrews told reporters on Sunday.
"Monash services more than a million people, it's a big health service and these upgrades are critically important."
The expansion will see additional birthing suites, birthing treatment spaces, medical surgical space and ICU with construction set to begin in 2025.
Victoria's healthcare system has been increasingly under pressure and struggling to keep up with demand during the COVID-19 pandemic.
Mr Andrews also recently proposed a $1 billion hospital upgrade in Melbourne's north, including Austin Hospital in Heidelberg and Northern Hospital at Epping.
Meanwhile, the Victorian opposition has proposed a legislated government debt cap to stop wasteful spending, if they win the state election in November.
An economic plan from the Liberal and Nationals parties would include placing a limit on spending to control state debt, which is predicted to hit $167 billion by 2025.
"We have more debt as a state today than NSW, Queensland and Tasmania combined," Opposition Leader Matthew Guy said on Sunday.
He added that interest on the state government's debt would reach more than $6 billion by 2025 which is "enough to build six Melton hospitals".
The debt cap legislation would prohibit any government from exceeding the legislated maximum without parliamentary approval.
The opposition didn't specify a level for the cap, saying this would be set once an accurate baseline debt level was known.
On Friday, Shadow Treasurer David Davis contacted the Department of Treasury and Finance requesting an urgent update on Victoria's balance sheet.
Mr Guy previously vowed to ditch the government's $35 billion Suburban Rail Loop and instead pour the money into Victoria's embattled health system.
Last month, a poll for The Age found Premier Daniel Andrews maintained a comfortable lead over Mr Guy as preferred premier by 46 per cent to 28 per cent.
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