The difference between having workers involved in their work, on the one hand, or too exhausted to contribute, on the other, can be tenuous and compromise work orientation. The positive outcomes of career calling (a deep purpose and meaningfulness in work characterized by vigor, dedication, and absorption) to organizations are clear, namely the relationship of career calling with high levels of commitment and engagement. However, the dark side of career calling remains a less explored point. The main purpose of this study analyzes this side of career calling and explores the relationship between sense of work purpose—perceived career calling—and workaholism. The sample consists of 743 Portuguese employees from different sectors of activity. The main hypothesis intends to test the presence of career orientation as a mechanism to explain the ambiguity of career calling outcomes, that is, the mediating effect of career orientation on the relationship between career calling and workaholism. The results showed that the workers’ career orientation helps to explain this relationship. Career orientation partially mediated the relation between career calling and the positive dimension of workaholism, involvement and enjoyment, and completely mediated the relation between career calling and negative dimensions of workaholism, drive. These results allow us to reflect on career calling, and how organizations manage workforce efforts to avoid work addiction and the negative consequences that compromise workforce sustainability. Career calling was looked at as an element of a mixed profile work orientation, rather than not just as a pure work orientation. Theoretical and practical implications are discussed.