Platinum-based chemotherapy remains the cornerstone of treatment for many malignancies. However, although therapeutic efficiency varies greatly among individuals, there is a lack of pharmacogenomic biomarkers that can be used in clinical settings to identify chemosensitive patients and allow stratification. With the development of high-throughput screening techniques and systems biology approaches, a growing body of evidence has shown that platinum resistance is a multifactorial, multi-dimensional, dynamic process incorporating genetic background, tumor evolution and gut microbes. This review critically summarizes potential pharmacogenomic biomarkers for predicting the efficacy of platinum drugs and provides a comprehensive, time-varying perspective that integrates multiple markers.