The Wnt signaling pathways are well known for having several pivotal roles during embryonic development. However, the same developmental signaling pathways also present key roles in cancer initiation and progression. In this chapter, several issues regarding the roles of both canonical and non-canonical Wnt signaling pathways in cancer will be explored, mainly concerning their role in the maintenance of cancer stemness, in the metabolism reprograming of cancer cells and in the modulation of the tumor microenvironment. The role of Wnt signaling cascades in the response of cancer cells to anti-cancer treatments will be also discussed, as well as its potential therapeutic targeting during cancer treatment. Collectively, increasing evidence has been supporting pivotal roles of Wnt signaling in several features of cancer biology, however; a lot is still to be elucidated.