The age of COVID-19 calls for a different approach toward global well-being and flourishing through the transcendence suffering as advocated by existential positive psychology. In the present study, we primarily explained what self-transcendence is and why it represents the most promising path for human beings to flourish through the transformation of suffering in a difficult and uncertain world. After reviewing the literature on self-transcendence experiences, we concluded that the model of self-transcendence presented by Frankl is able to integrate both of the characteristics associated with self-transcendence. Afterward, we discussed how the self-transcendence paradigm proposed by Wong, an extension of the model by Frankl, may help awaken our innate capacity for connections with the true self, with others, and with God or something larger than oneself. We presented self-transcendence as a less-traveled but more promising route to achieve personal growth and mental health in troubled times. Finally, we presented the history of the development and psychometrics of the Self-Transcendence Measure-Brief (STM-B) and reported the empirical evidence that self-transcendence served as a buffer against COVID-19 suffering. The presented data in the current study suggested that the best way to overcome pandemic suffering and mental health crises is to cultivate self-transcendence.