The region covers the southeastern part of the main island of Malta.

The region borders the Northern, Eastern, Port and Western Regions.

XIV of 2019, which led to a regional reform in 2021, significantly altered the region's borders and composition, and reduced its local councils from 14 to 12.

Southern Region includes parts of the Northern Harbour District, South Eastern District and Southern Harbour District.

Southern Region includes 12 local councils: After the 2021 local government reform, the region ceded 6 of its local councils to the newly established Western region: The current Southern Regional Counsil (Maltese: Kunsill Reġjonali Nofsinhar) is made up of:[2]