Immune checkpoint inhibitors (ICIs) therapy has steered in a new era of anti-tumor therapy, with significant survival outcomes observed for multiple tumors. Anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) antibody has been approved for second-line or first-line treatment in melanoma, lung cancer, renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC) and gastroesophageal cancer. However, despite the breakthrough in clinical treatment with ICIs, most patients do not benefit. As an example, pembrolizumab or nivolumab showed 40–45% response as a first-line treatment in melanoma patients and 20% response as a second-line treatment in non-small cell lung cancer (NSCLC) patients. Therefore, attention has given to identifying and validating predictive biomarkers for the efficacy of ICIs. Liquid biopsy (the use of biomarkers in body fluids in place of traditional tumor tissues) approached has also been investigated as potential predictive biomarkers. In recent years, the tumor microenvironment, tumor genome through next generation sequencing, and neoantigens have been investigated to comprehensively understand tumour biology. The field is now moving towards multi marker predictive panels in place of single marker as previously done. The advent of single cell RNA sequencing and 3D spatial biology technology will fast track the progress of identifying predictive biomarkers to stratify cancer patients who are responders vs non-responders for ICT treatment.