This study explores the integration of Information and Communication Technology (ICT) and Indigenous Knowledge Systems (IKS) to enhance student well-being in STEM classrooms within South African higher education. South Africa has long struggled with low enrolment and poor performance in STEM subjects, impaired by inadequate teacher training, teaching methodologies, and psychological factors such as anxiety. The COVID-19 pandemic has further emphasized the need for resourcefulness in education, highlighting the potential benefits of technology and indigenous knowledge in mitigating these challenges. The researchers investigate the synergy between ICT and IKS in reducing stress and anxiety among STEM students and educators. The study employs a critical reflective approach to analyze existing literature and derive a preliminary framework. This framework includes criteria for integrating IKS into STEM curricula, strategies for using ICT and IKS synergistically, and professional development for STEM teachers in the era of decolonization and the Fourth Industrial Revolution (4IR). The study concludes by proposing twelve preliminary criteria for the effective use of ICT and IKS to address psychological challenges in STEM education. These criteria aim to promote a holistic, inclusive, and culturally relevant learning environment that leverages both traditional knowledge and modern technological advancements. However, the study’s reliance on theoretical perspectives without empirical testing may affect the validation of the proposed criteria.