Background: Small and medium-sized enterprises (SMEs) play a crucial role in driving economic growth and development, necessitating innovative strategies to enhance their sustainability and resilience in an ever-evolving business landscape. The evolving business landscape requires innovative strategies for SMEs’ sustainability and resilience. Recognising this imperative, the strategic incorporation of Tshivenda Indigenous Knowledge Systems (IKS) within SMEs emerges as a compelling avenue for exploration.Aim: This study aims to provide insights into the challenges and opportunities faced by SMEs concerning the adoption of Tshivenda IKS to foster business sustainability.Setting: The study focused on Tshivenda IKS as practised by SME owners who are Tshivenda speakers, located in Musina, Limpopo, South Africa, and in Beitbridge, Matabeleland South, Zimbabwe.Methods: The study used qualitative research with a grounded theory design, interviewing 12 participants selected through theoretical sampling. Thematic coding was applied for data analysis.Results: The study identifies greater collaboration, access to markets, brand differentiation and competitive advantage as opportunities, whereas cultural differences, a lack of strategic planning, and shortages in sustainable supply chains were identified as key challenges to SMEs incorporating Tshivenda IKS in their business operations.Conclusion: The study sheds light on the challenges, opportunities and managerial implications associated with integrating Tshivenda IKS into SMEs for sustainability purposes. Leveraging Tshivenda IKS offers substantial opportunities for sustainable business practices and economic development in SMEs, despite the limitations.Contribution: The study enriches understanding of the opportunities and challenges experienced by SMEs when using Tshivenda IKS in fostering business sustainability.