Continuous blood pressure (BP) measurement is crucial for long-term cardiovascular monitoring, especially for prompt hypertension detection. However, most of the continuous BP measurements rely on the pulse transit time (PTT) from multiple-channel physiological acquisition systems that impede wearable applications. Recently, wearable and smart health electronics have become significant for next-generation personalized healthcare progress. This study proposes an intelligent single-channel bio-impedance system for personalized BP monitoring. Compared to the PTT-based methods, the proposed sensing configuration greatly reduces the hardware complexity, which is beneficial for wearable applications. Most of all, the proposed system can extract the significant BP features hidden from the measured bio-impedance signals by an ultra-lightweight AI algorithm, implemented to further establish a tailored BP model for personalized healthcare. In the human trial, the proposed system demonstrates the BP accuracy in terms of the mean error (ME) and the mean absolute error (MAE) within 1.7 ± 3.4 mmHg and 2.7 ± 2.6 mmHg, respectively, which agrees with the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). In conclusion, this work presents a proof-of-concept for an AI-based single-channel bio-impedance BP system. The new wearable smart system is expected to accelerate the artificial intelligence of things (AIoT) technology for personalized BP healthcare in the future.