If your audience is primarily from specific regions, ensure the program offers good ad fill rates and competitive pricing for those locations. Some networks perform better with US/UK traffic, while others excel in other regions.
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Revenue Sharing Model
Understanding how revenue is split between you and the network is crucial. Some programs offer 70-80% revenue share, while others provide fixed rates per click. You can calculate how much potential earnings are based on the traffic patterns and choose accordingly.
Ad quality and user experience
It's something that most guides won't tell you: If the ads suck they will kill your site faster than you can get out of it. Its even people who destroy their organic traffic by chasing a few extra bogus ads.
Look for programs that can offer high-quality, and relevant advertisements when they don't drive away your audience. Having poor ad quality can hurt the sites reputation and SEO rankings.