Evidence about the characterization of home workers in terms of both work-related outcomes and health issues is lacking. The purpose of this cross-sectional study was to examine the impact of home working on perceived job productivity and satisfaction, work-related stress, and musculoskeletal (MSK) issues. We included 51 mobile workers, collecting data about demographic characteristics, working experience, job productivity, and stress. Job satisfaction was assessed through the Utrecht Work Engagement Scale (UWES), while MSK pain was investigated by the Brief Pain Inventory (BPI) and Fear Avoidance Beliefs Questionnaire (FABQ). Moreover, a home workplace analysis had to be carried out according to current Italian regulations. Participants declared that they were less productive (39.2%) but less stressed (39.2%) and equally satisfied (51%) compared to the time of office working. Regarding MSK disorders, low back pain (LBP) was referred by 41.2% of home workers and neck pain by 23.5% of them. Neck pain worsened in 50% of home workers, while LBP did not exacerbate in 47.6% of cases. Home workers with MSK pain reported a lower job satisfaction. Depending on our data, the home environment seems to be not adequate in the mobile worker population, with an increased risk for mental health and MSK problems, particularly affecting the spine. Addressing these issues can significantly reduce risks for health, thus, improving job productivity and satisfaction and reducing cost.