Organizations are operating in a VUCA world, punctuated by volatility, uncertainty, complexity, and ambiguity. Recent technological developments have given rise to new jobs, new demands, new products, new processes, new work arrangements, and new methods of service delivery thus significantly disrupting workplaces and creating a need for new workplace skills. There is a growing anticipation of “new normals” characterized by skills revolutions, among other factors. Such a context poses serious challenges to human resource management in regard to developing and maintaining a competitive advantage amidst volatility, uncertainty, complexity, and ambiguity. The aim of this theoretical study was to assess the need for upskilling and reskilling and propose an organizational sense-response framework for upskilling and reskilling in a VUCA business world. The findings show that for any organization to ensure sustainability in the VUCA world, it must focus on its most valuable asset— its people. Organizations need to strategically develop employees’ skills based on organizational objectives. In such a dynamic world, people require competencies in different skills including but not limited to technological skills, self-management skills, social and cross-cultural skills, cognitive skills, entrepreneurial skills, and mastery of 21st century inter-disciplinary themes to exhibit good performance. The future of work is therefore likely to focus on continuous upskilling and reskilling people to be able to thrive amidst constant disruptions. The proposed framework shows that organizations need sensing and response capabilities for them to thrive amidst rapid change, especially in the external environment. The sensing capability ensures that organizations continually maintain awareness of external threats or opportunities. The response capability, on the other hand, ensures that organizations are able to determine how best they can adapt to changes, after assessing the relevance of those changes to their organizations’ current situations and long-term strategic objectives, as well as the possible benefits and threats of those changes.