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This study investigates the impact of telework intensity on the work exhaustion experienced by hospital administrative staff, with a particular focus on the emotional dimension of this phenomenon and the mediating role of both positive and negative interactions between the work and personal life domains. Grounded in the Job Demands–Resources (JD-R) model, the research underscores the ambivalent nature of teleworking: While it can serve as a protective factor against emotional exhaustion, it may also increase job demands, thereby influencing occupational health outcomes. Data were collected through a questionnaire administered between January and May 2023, and the findings were analyzed using structural equation modeling. The results indicate that greater telework intensity is directly associated with a reduction in emotional exhaustion. However, teleworking also has indirect effects mediated by work–life interactions. On one hand, it fosters positive spillover between professional and personal life, which mitigates emotional exhaustion. On the other hand, it intensifies negative interference of personal life into work, thereby exacerbating emotional exhaustion among teleworkers. These findings highlight the strategic importance of managing telework in a way that enhances its protective benefits while minimizing its potential drawbacks. Although teleworking can act as a valuable tool for promoting occupational health, it may simultaneously exacerbate interdomain conflicts—particularly through increased personal-to-work interference, a key driver of emotional strain. From a managerial standpoint, these findings should prompt hospitals to implement training programs and support mechanisms tailored to both teleworkers and their supervisors. Tailoring boundary management policies to the specific needs of staff appears essential for optimizing the advantages of telework and mitigating its adverse effects.