The COVID-19 pandemic has caused a worldwide disruption. Most people have never witnessed such a global threat, and the world’s leaders have not dealt with a crisis of this magnitude; moreover, Research & Innovation (R&I) teams have little time to invent new pharmaceutical therapies. Nations are trying to implement controlling strategies for avoiding significant losses, but this pandemic has already imprinted itself upon their citizens’ psyche, created social anxiety, and disrupted national economies. The complexity of the psychological, social, and economic interrelations of this new source of stress cannot be appropriately understood by scientific reductionism and specialised thinking only. It needs to be considered how the current pandemic links to questions of ecological sustainability and resilience. Further, we must rethink the complex interactions of human-nature health that drove the crisis, as proof of an unsustainable human civilisation. Accordingly, this paper aims to contribute to the transdisciplinary resilience dialogue on the health maintenance and life-supporting processes of the biosphere by focusing on the COVID-19 crisis. It explores various frameworks that are contributing to the transdisciplinary meta-perspective of resilience. Moreover, it proposes a humanistic approach based on not only controlling strategies involving containment and social isolation but also the ecological balance considering the human, societal, and ecological health as a system-wide emergent property. Conceptual frameworks of resilience are discussed—as mapping methodologies to structure the discourse—focusing on the role of leadership and empowerment. Furthermore, some positive insights are discussed, as a transdisciplinary integrator and solidarity facilitator of coping, mitigation, and decision-making in the time of uncertainty and anxiety created by the COVID-19 pandemic.