In conditions of external challenges, each region reacts to changes in a special way, which determines the heterogeneity of adaptations. The aim of the article is to analyze the methodological features of assessing regional heterogeneity of adaptation to the impact of external challenges. Accordingly, the subject of the study is the consideration of the peculiarities of regional heterogeneity of adaptation to external challenges. Drawing on the analysis of scientific literature, the author systematizes and discloses the groups of approaches concerning various aspects of regional adaptation and assessment of its heterogeneity in terms of: adaptations to future changes as a result of digitalization and automation; economic development of regions and financial provision of the population's interests; spatial features of regional development; creation of conditions for population adaptation and implementation of adaptation opportunities. Based on the results of the study, the author identifies methodological features of the assessment, taking into account: the characteristics of the challenge of the external environment, the level of provision of territories with adaptive capabilities, the manifestation of new elements and structures that characterize the changing environment, their inconsistencies with the management context of regional development, the ability of the regional management system to cope with the relevant changes by optimizing regional management on the basis of a targeted impact on the priorities of the elements of the system. The author proposes the use of indicative assessment methods for the implementation of adaptation as a management function, based on the achievement of target development indicators (set by various development programs and projects), which would ensure the selection of priorities and the development of measures to increase the adaptive capacity of regions in order to improve the directions of the state policy of regional equalization. The results obtained may be in demand for further research concerning the study of regional processes and the substantiation of specific forms and mechanisms of adaptation, as well as the development of a methodology for assessing regional heterogeneity of adaptation.