Regional prosperity depends on several factors while resilience appears as one of the most important determinants in recent decades. It is thus an ability to adapt to the threats and challenges that economic development brings. Such a threat was also the crisis manifested in the last years of the last decade. An extensive amount of analyses deals with the ability of regions to respond to these changes or to adapt to new trends. A significant part of the current literature addresses the role of innovation, which is seen as a key factor of economic development starting with Schumpeter’s theory to the current role of Smart Specialization. The present chapter deals with resilience in the context of innovation activity in regions of the Slovak Republic. As innovations in Slovakia are by a critical mass supported from the resources of the European Union, this work analyses the innovation support in terms of resilience on coming trends of economic development.