Tourism, with a high economic and social significance for the economy of many countries, is one of the fastest developing fields. A new challenge of transition to an innovative way of developing tourism industry is strongly proposed with the result of existing conditions of fierce rivalry in the field, economic and political instability in many regions, including the Republic of Uzbekistan, the fast-growing needs and demands of tourists. Therefore, destinations, importantly, have to determine their competitiveness to figure out their strengths and weaknesses and thereby develop their future conditions. The authors discuss the issues related to the innovation in tourism destinations and present its main directions in the sector, as well as factors affecting the innovative development of the fieldin Khorezm region of Uzbekistan. Moreover, the chapter illustrates the principles and basic requirements for the system of managing innovative activities in tourism destinations at macro, mesa, and microeconomic levels.