There is no universal innovative strategy that could fit every digital enterprise in the regions. When forming an innovative strategy of digital enterprises, regions should take into account market demand generated by small, medium-sized (SMEs) and large enterprises. The share of large enterprises (5%) is much smaller in the world in relation to the number of SMEs (95%). In most countries (38 out of 43), the number of large enterprises is less than 0.01%. Correlation coefficients (calculated according to the Kendall method and the Spearman method) showed an average level of associations between innovation activity of digital enterprises in the region and the size of enterprises (small and medium-sized enterprises and large enterprises). Deviations from the supply and demand in the market of innovations of digital enterprises are determined using the scoring method in 43 regions. The researchers proposed a classification of five strategies of innovative activity of digital enterprises in the region. The criteria for classifying strategies included: priority of innovations of digital enterprises in the national market; deviation in demand and supply in the market of technologies for the digital enterprises; class of innovative activity of the digital enterprises in the region. Regions of the high level of innovation activity apply a strategy of introducing innovations at SMEs and large enterprises in the domestic market. Most regions have a 74% shortage of demand in the domestic market (except for China, India) and apply an implementation strategy based on the external market, without priority to a certain size of the enterprise. A well-chosen strategy contributes to the growth of the introduction of patents of digital enterprises, without disturbing the balance between SMEs and large enterprises to achieve sustainable development goals in the regions. Starting from 2022, regions are recommended to revise the innovation strategies. This is necessary due to the transition of regions to the development of domestic markets due to the reduction in foreign trade.