The article discusses the evolving landscape of biomarkers for checkpoint inhibitor immunotherapy, focusing on the factors influencing response, resistance, and adverse effects. It highlights the role of tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels, and the tumour microenvironment, including the gut microbiome. Recent research emphasizes the importance of molecular and cellular determinants of response, aiming to optimize precision immunotherapy. Key factors include tumour antigens, mutation burden (TMB), neoantigens, and specific genetic mutations. TMB is associated with ICI response, but other factors like tumour heterogeneity, mutation signatures, and immune checkpoint molecules also play a role. The article also explores the impact of patient germline genetics, particularly HLA diversity, on ICI response. The immune microenvironment, including PDL1 expression, tumour-infiltrating lymphocytes (TILs), and immune-inflamed, immune-excluded, and immune-desert phenotypes, is crucial for predicting ICI outcomes. The study underscores the need for dynamic biomarkers and a deeper understanding of tumour–host interactions to improve ICI efficacy and patient outcomes.The article discusses the evolving landscape of biomarkers for checkpoint inhibitor immunotherapy, focusing on the factors influencing response, resistance, and adverse effects. It highlights the role of tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels, and the tumour microenvironment, including the gut microbiome. Recent research emphasizes the importance of molecular and cellular determinants of response, aiming to optimize precision immunotherapy. Key factors include tumour antigens, mutation burden (TMB), neoantigens, and specific genetic mutations. TMB is associated with ICI response, but other factors like tumour heterogeneity, mutation signatures, and immune checkpoint molecules also play a role. The article also explores the impact of patient germline genetics, particularly HLA diversity, on ICI response. The immune microenvironment, including PDL1 expression, tumour-infiltrating lymphocytes (TILs), and immune-inflamed, immune-excluded, and immune-desert phenotypes, is crucial for predicting ICI outcomes. The study underscores the need for dynamic biomarkers and a deeper understanding of tumour–host interactions to improve ICI efficacy and patient outcomes.