Fatigue estimation for critical structures necessitates comprehensive monitoring, which, in turn, requires dense instrumentation and models that heavily rely on computational resource. However, the fatigue vulnerability of different segments within the infrastructure can be considered to adopt a cost-effective substructure-based monitoring approach, minimizing the need for extensive instrumentation or complex models. However, estimating or instrumenting the substructure boundary adds to the complexity. In addition, conventional fatigue estimation approaches often assume constant structural health, disregarding the unknown current health status of aging structures. To overcome this limitation, a novel substructure-based fatigue life estimation approach is developed, incorporating an interacting ensemble-particle filter that considers the current health status while remaining robust against boundary forces. Numerical experiments validate the proposed approach on a simulated reinforced concrete box girder bridge, utilizing a 3D beam model that accounts for dynamic interaction with vehicles. A parametric analysis investigates the relationships between fatigue damage and factors such as surface roughness, vehicle speed, vehicle weight, and vehicle category, aiming to identify dominant stimuli. The results demonstrate an accurate estimation of health parameters and remaining useful life (RUL). Furthermore, a novel decomposed approach for RUL estimation is developed, enabling the mapping of traffic information to fatigue damage without requiring costly simulations. A case study highlights the practical applicability of the approach, focusing on a reinforced concrete box girder bridge in Himachal Pradesh, India.