Scholars often examine the effect of generic job demands and resources on burnout, yet to increase ecological validity, it is important to examine the effects of occupation-specific characteristics. An extended version of the job demands-resources model with work−home interference as a mediator is examined among a cross-sectional sample of 178 general practitioners (GPs). Interviews with GPs were used to develop questions on occupation-specific work characteristics. Hypotheses were tested in MEDIATE. Both generic and occupation-specific job demands positively affected emotional exhaustion, while only occupation-specific job demands affected depersonalization. Only strain-based work−family interference mediated the relationship between generic and occupation-specific job demands, emotional exhaustion and depersonalization. This study offers an important extension of the job demands-resources model by including occupation-specific job characteristics. This broader perspective can aid in more targeted job design to reduce burnout among GPs.