Two studies were conducted to examine how home healthcare nurses stay engaged in their work and maintain their psychological well-being. In Study 1, we hypothesized that nurses would perceive work pressure more as a hindrance demand than as a challenge demand, and that the reverse would be true for emotional demands. We approached 120 home healthcare nurses who filled in a survey. Results of a series of paired sample t-tests supported our hypotheses. In Study 2, we used the JD-R model to hypothesize that weekly job demands can either facilitate or undermine the positive impact of personal resources on work engagement and flourishing, depending on the nature of the job demand (hindrance vs. challenge). A sample of 63 nurses filled in a questionnaire at the end of the working week during three consecutive weeks (N = 3 × 63 = 189 occasions). Results of hierarchical linear modeling showed that emotional job demands strengthened the effect of personal resources on weekly well-being, whereas work pressure undermined this effect. Taken together, the present findings challenge the idea that whether job demands act as hindrances or challenges is the same for all occupations and for all individuals.