This study summarizes stakeholders’ preferences for promoting economic growth by facilitating sustainable businesses and entrepreneurship in economically distressed regions in South Carolina. A survey was conducted in a randomly selected rural county and an urban county to capture stakeholders’ preferences for pathways to bolster economic development. Thus, the survey captured stakeholder perceptions regarding challenges and opportunities of economic and entrepreneurial development including any regional dynamics associated with a rural and an urban community. The survey responders represented various stakeholder groups including local business owners, executives, public officials, officials of non-profit organizations. The survey recorded stakeholders’ feedback on pertinent questions including economic and entrepreneurial development challenges and opportunities, environmental sustainability, skills-enhancement training to increase employability of residents, and public-private partnership opportunities. Study results will convey multi-sector stakeholders’ perceptions and suggestions as insights for urban and regional economic development practitioners, policymakers, and academicians. Besides, the results of this study will be useful for anyone interested in economic and entrepreneurial development in South Carolina, especially those focused on sustainable growth in areas that include census tracts designated as Qualified Opportunity Zones (QOZs).