<p>In-service remanufacturing of machine tools refers to an active remanufacturing strategy that aims to achieve optimal remanufacturing performance and economic benefits at the most appropriate timing. As a critical approach to maximizing resource utilization efficiency, it has significant implications for sustainable manufacturing. However, for the spindle of in-service machine tools—characterized by high stability and long service life—the determination of its remanufacturing time domain remains a challenging issue. To address this problem, this study proposes a time domain decision method for machine tool spindle remanufacturing based on residual life prediction. Specifically, the research proceeds as follows: first, a nonlinear fatigue damage-based residual life prediction model for in-service machine tool spindles is established, with the interaction effect between multi-source loads fully considered. Second, based on the residual life prediction and the spindle degradation mechanism, a two-stage Wiener process model is constructed and its reliability analyzed. Third, the Schwarz Information Criterion (SIC) is adopted to estimate the turning point of machine tool degradation, thereby establishing a time domain decision mechanism for in-service machine tool spindle remanufacturing. Finally, a case study on a machine tool spindle is conducted to calculate and simulate the in-service remanufacturing timing. The results demonstrate that the proposed method can determine a more accurate in-service remanufacturing time for machine tool spindles, providing a theoretical basis and practical reference for the selection of in-service machine tool remanufacturing timing. </p>