Ensuring optimal performance and reliability in rotor-bearing systems is crucial for industrial applications. Imbalances and shaft bowing in these systems can lead to decreased efficiency and increased vibrations. The early detection and mitigation of a rotor’s faults are essential, and model-based fault identification has gained much attention in the manufacturing industry over the years. Over the past two decades, however, the development of fault diagnosis rules with data-driven and artificial intelligence (AI) methods has become a trend, and in the foreseeable future the combination of AI with big data will become mainstream. Nevertheless, the critical role of rotating machinery in manufacturing introduces a challenge, as often insufficient fault data are available. This limitation renders the establishment of diagnostic rules using data-driven methods and AI technologies impractical. In light of these challenges, this study proposes a novel hybrid approach that combines a physical model with machine learning (ML) techniques for the diagnosis of multi-faults (imbalances and shaft bowing are demonstrated) in a Jeffcott rotor. To overcome the lack of real-world labeled fault datasets, a physics-based Jeffcott rotor model is first derived and then used to generate abundant fault datasets for ML. Subsequently, simulated data are employed for the training of an artificial neural network (ANN), enabling the network to learn from and analyze the vast array of generated data. The results prove that a well-trained feed-forward neural network (FNN) can accurately isolate and diagnose imbalance and shaft bowing faults using the simulated and real data from the Jeffcott rotor experiment. These physics-based and ML approaches prove effective particularly for multi-faults, offering new possibilities for advanced rotor system monitoring and maintenance strategies in industrial applications.