The NSE will ease the growing traffic along the north-south corridor currently served by only the Central Expressway (CTE).
But, the greater convenience for motorists will mean disruption to several property owners.
In a massive acquisition exercise, the Government will have to acquire some 40 lots and over 30 partial lots of land for the construction of the NSE.
This means that houses along Marymount Terrace, as well as several properties on the Marymount Convent site including the Orange Valley Nursing Home, the Good Shepherd Chapel and Rose Villa, will have to relocate.
However, Marymount Kindergarten and Marymount Convent School will remain where they are.
Work on the new expressway, which runs parallel to the CTE and will also connect to existing expressways such as the Seletar Expressway, is expected to begin in 2013 - and that is the deadline for the properties to move.
Responding to media queries, the Singapore Land Authority and Land Transport Authority (LTA) said in a joint statement: "All owners whose properties are affected by the acquisition will be given two years from the date of acquisition to vacate the premises."
Residents at Marymount Terrace who spoke to MediaCorp said they have received the acquisition notices and have little option but to move.
One of them, Ms Joseph Esther, said she will be looking for a new home.
Another resident, who declined to be named, said he was getting his property evaluated before entering into discussions with the authorities on compensation.
The congestion on the CTE, especially during peak hours, has been a perennial complaint among motorists.
According to LTA, even with the completion of the CTE-widening project by the end of this year, traffic along the north-south corridor is expected to continue to grow. It added that the NSE will help ease traffic on major arterial roads, such as Thomson Road and Marymount Road.
The Urban Redevelopment Authority said the sites at Marymount Terrace and Marymount Convent will be considered for residential development after the completion of the new expressway.