In the era of Industry 4.0, digital human modeling (DHM) may be the key to improving ergonomics related to manual operations in the workplace. Poor workplace ergonomics may lead to reduced work productivity and an increased risk of health problems among employees, resulting in actual losses for enterprises, e.g., sickness absence, employee turnover, and training. DHM technology can help speed up ergonomic analysis and improvement. This paper proposes a methodological framework based on DHM to improve ergonomics in the workplace. Its purpose is to provide practitioners with an easy and detailed approach to ergonomics assessment and improvement procedures. The framework developed two main stages: the workplace Research Stage and the DHM and Simulation Stage, which cover the eight detailed steps of an effective DHM-based ergonomic assessment together. A case study was used to verify and demonstrate the effectiveness of the proposed methodological framework.