Cross-project defect prediction (CPDP) leverages machine learning (ML) techniques to proactively identify software defects, especially where project-specific data is scarce. However, existing CPDP approaches suffer from three critical limitations: ineffective exploration of high-dimensional parameter spaces, poor adaptability across diverse projects with heterogeneous data distributions, and inadequate handling of feature redundancy and distribution discrepancies between source and target projects. To address these challenges, we formulate CPDP as a multi-objective bilevel optimization (MBLO) method, dubbed MBL-CPDP. Our approach comprises two nested problems: the upper-level, a multi-objective combinatorial optimization problem, enhances robustness by optimizing ML pipelines that integrate feature selection, transfer learning, and classification techniques, while the lower-level problem fine-tunes their hyperparameters. Unlike traditional methods that employ fragmented optimization strategies or single-objective approaches that introduce bias, MBL-CPDP provides a holistic, end-to-end optimization framework. Additionally, we propose an ensemble learning method to better capture cross-project distribution differences and improve generalization across diverse datasets. An MBLO algorithm is then presented to effectively solve the formulated MBLO problem. To evaluate MBL-CPDP’s performance, we compare it with five automated ML tools and 50 CPDP techniques across 20 projects. Extensive empirical results show that MBL-CPDP outperforms the comparison methods, demonstrating its superior adaptability and comprehensive performance evaluation capability.