CD70, which is a ligand belonging to tumour necrosis factors, exhibits aberrant overexpression among multiple hematologic and solid malignancies and has drawn extensive research enthusiasm as a target to treat and diagnose cancers. CD70-targeted immuno-PET/CT is an emerging approach for cancer diagnosis, with the potential to improve tumour detection, assist disease staging, and monitor therapeutic response. CD70-targeted therapeutic approaches, involving antibody-drug conjugates, CAR-T, CAR-NK, and monoclonal antibodies, have shown encouraging activity in preclinical models and preliminary signals of efficacy in early clinical studies. In addition to these monotherapies, increasing efforts have focused on rational combination strategies that aim to enhance antitumor efficacy, reverse immune suppression, and overcome resistance. This review comprehensively summarizes the diagnostic and therapeutic advances in CD70-targeted strategies, discusses ongoing barriers, and outlines future directions to advance CD70-targeted imaging and therapeutic strategies through mechanistic research and clinical translation. Key points CD70 is aberrantly overexpressed in diverse malignancies with limited normal tissue expression. CD70-targeted immuno-PET/CT improves tumour detection, staging, and treatment monitoring. Multiple CD70-targeted therapies, including CAR-T and CAR-NK, are under active investigation. Rational combination strategies are emerging to enhance antitumor efficacy.