Background: The study aimed to assess the health-related quality of life (HRQoL) and its associated factors among urban slum dwellers who migrated from different rural parts of Bangladesh. Methods: The present study analyzed data from a Migration and Mobility Determinants on Health survey and was conducted in 2017 among 935 migrant slum dwellers of Dhaka city (North & South) and Gazipur City Corporations, as a part of the icddr,b’s Urban Health and Demographic Surveillance System (UHDSS). The face-to-face interviews were conducted with the adult population by using a semi-structured questionnaire that included variables related to socio-demographics, migration, occupation, and HRQoL (SF-12). Bivariate and multiple linear regression analyses were performed to determine the factors associated with HRQoL. Results: The mean (±SD) scores of physical component summary (PCS), and mental component summary (MCS) were 57.40 ± 22.73 and 60.77 ± 22.51, respectively. As per multiple regression analysis, lower PCS scores were associated with having older age, being female, and not having any job. Mean MCS scores were significantly lower among participants who reported having older age, not having any job, not working/ less working hours (≤8 h/day), as well as increased work-related stress in the current urban slum. Conclusions: The findings suggest that available urban social protection programs should include a comprehensive social safety net for the improvement of the slum infrastructure as well as proper health care and risk mitigation plans at workplaces.