Exogenous regional development approaches had failed to deliver turn-around in the declined space-economies of most administrative regions in Ghana. The relatively poor Central Region decided to embark on an endogenous regional development intervention, including the establishment of its own development company, Central Region Development Commission (CEDECOM) to manage the process and successfully implemented three innovative strategic programmes during the 1990/1991 to 2000/2001 periods. Following these, however, CEDECOM ended its original mandate and considered it necessary to reposition and refocus on business and enterprise development and investment promotion. The study aimed to explore, analyse and reflect on how CEDECOM managed this context, based on its repositioning, internal organisational structure, enterprise development and business focus, corporate environment, organisational and competitive performance. Literature review was used to derive concepts of exogenous and endogenous regional development processes, the latter theoretically modelled, based on 9 main factors, focused on business and enterprise development and investment promotion, all involving secondary qualitative material. An in-depth field interview was undertaken with key officers of CEDECOM and the regional governance body about the Commission’s general practices and repositioned and reemphasised approaches, producing primary and qualitative data. A StrengthWeakness-Opportunity-Threat model was used to assess the competitive and corporate environment of CEDECOM. CEDECOM’s performance based on the identified factors was largely limited and questioned the effectiveness of its repositioned and reemphasised approaches. It became less competitive due to these and its weak financial position, compared with its competitors, hardly succeeding in effectively promoting the regional competitiveness. Concluding, CEDECOM needed to secure explicit legislative backing, streamlined governance, adequate funding, effective co-operative and collaborative engagement, independent decision-making, planning and implementation, expanded demonstration projects to scaled-up commercial investment activities, focusing MSME support on the indigenous resource base, making its competitive scope more practical, and promoting sustainability, relatedly informing future regional policy