How they really differ
MailerLite focuses on doing email well and simply. Systeme.io covers more of the business, from first page to payment, with email as one piece.
If you sell through Shopify, Gumroad or a separate course platform, MailerLite connects to it. If you want everything in one place, Systeme.io avoids the glue work.
Using both
Most people pick one. Running both duplicates email features, so only do it if you have a clear reason.
The verdict
Email-focused small businesses: MailerLite. Solo creators selling courses or digital products who want one tool: Systeme.io.
Want the full write-up on each? Read our MailerLite review and Systeme.io review.