Background: Although common work conditions cannot be clearly classified as positive or negative, previous challenge-hindrance demands scales have failed to address this issue. Objective: The purpose of this study was to develop and validate scales that allow the assessment of perceived levels of challenge-hindrance demands in the nursing profession and that are in conformance with the nature of the construct. Design: The study employed an exploratory sequential mixed-methods design, composed of two phases. Firstly, the qualitative method was employed to find out the common work environment that is typically linked to the job demands of nurses; new scales were generated following the results. Secondly, the quantitative method was employed to refine and assess the validity and reliability of the instruments. Participants: The key informants for the interview were 11 registered nurses from seven private hospitals in Bangkok, Thailand. In addition, the sample of the quantitative study, consisting of 761 Thai nurses from 16 private hospitals in Bangkok was randomly divided into three parts for different analyses (i.e., exploratory factor analysis, confirmatory factor and reliability analysis, and nomological validity analysis). Results: The findings demonstrated that the assessment of the challenge-hindrance demands consists of three parts: The amount of experience with stressors, the appraisal of challenges, and the appraisal of obstacles. The analyses led to the creation of two scales: the challenge demands scale and the hindrance demands scale, each with 14 variables and four dimensions. Conclusions: The separation of the scales into three parts made it evident that, since job demands themselves are part of an inevitably stressful work environment, hospitals have to focus on the individual interpretation of each job demand in order to manage the burnout and engagement of nurses. In addition, the scales have potential use in studies relevant to problems encountered in the nursing profession (e.g., opting to pursue a different career).