It will examine a range of issues, including valuations, disposal strategy and conflicts of interest.
Nama is the Republic's "bad bank", established in 2009 in the aftermath of the Irish banking and property crisis.
It took effective control of a huge property loan book in Northern Ireland and formed a committee to advise on that part of its portfolio.
Nama sold its entire Northern Ireland portfolio to Cerberus, a US investment fund, for £1.2bn in 2014.
There have been a series of allegations about impropriety in the sales process.
The decision to set up the commission was agreed by Taoiseach (prime minister) Enda Kenny and  opposition parties.
A final report is due at the end of 2017 and an interim report is expected within three months.
At Stormont on Wednesday, Finance Minister Máirtín Ó Muilleoir will be questioned over what he knew about secret contacts between a former Sinn Féin MLA and a loyalist blogger.
Mr Ó Muilleoir is due to appear before Stormont's finance committee, where he will answer questions about Nama coaching allegations.
The Republic of Ireland is to set up a Commission of Investigation into Nama's sale of its Northern Ireland loans.