There are multiple ways to do it.
You can have a sales team selling your premium ad inventory directly to advertisers and media agencies. It will allow you to earn higher CPM. However, in order to do this, one has to have a valuable audience and good inventory quality on their site. But there still remain enough remnant inventory unsold.
Second option is to monetize inventory selling through programmatic auctions. This will help you to sell a bigger part of your inventory.  Combination of both options will provide the best result and maximize your ad revenue.