The Associated Newspapers title plans to simplify its structure by cutting the number of main sections from four to two.
These will be distributed alongside its magazines, You and Live!.
In addition to the main section, which will combine news with revamped financial coverage, The Mail on Sunday will introduce a second section called "2.0", featuring entertainment, health, sport and national property.
The planned changes, expected to be introduced on 13 January, were announced internally last week, and the newspaper's ad team is expected to talk to agencies about the innovations over the coming weeks.
Agencies have welcomed the idea of the changes but have yet to discover how they will impact on ad rates. One press director said: "It's great they're investing in content, and we'll have more opportunity to advertise in key sites. However, there will probably be a premium attached to it."
The Mail on Sunday is performing relatively well in the newspaper market.
Its September circulation was flat at 2,348,982, but initiatives such as its free Prince CD covermount giveaway have helped to create circulation spikes on specific issues.
Simon Davies, the advertising director at The Mail on Sunday, was unavailable for comment.