The aim of this report is to describe the innovation activities, the nature and patterns of interaction among innovation actors as well as the extent of the availability of infrastructure that supports innovation in four districts (i.e., Namakwa, Pixley ka Seme, Sarah Baartman and Central Karoo) in the Karoo region. This study was commissioned by the Department of Science and Innovation to inform the development of an innovation strategy for the region, in support of the Small Town Regeneration and Regional Economic Development (STR/ RED) initiative. The STR/RED initiative is a flagship programme of the South African Local Government Association (SALGA), which was launched in 2013 across the country. The STR/ RED programme, while targeting the revival of small towns in the region, adopts a regional economic approach, focusing on the optimal use of available resource to exploit identified regional opportunities to stimulate economic growth, job creation and spatial transformation in the region. The DSI seeks to centralise innovation as a key pillar of the STR/ RED initiative.