Immune checkpoint blockade targeting the novel targets of the lymphocyte activation gene 3 (LAG3) and the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) has marked a significant advancement in oncology, offering new therapeutic opportunities to fight diverse malignancies. This review covers the biological basis and clinical application of LAG3 and TIGIT inhibitors, highlighting pivotal trials and therapeutic outcomes. We underscore the use of dual therapy immune checkpoint blockade in enhancing antitumor immunity, particularly in settings where monotherapy has shown limited efficacy. Additionally, we address the emerging challenges such as treatment resistance and adverse effects. We explore the strategic integration of LAG3 and TIGIT blockade within the broader immunotherapy landscape, emphasizing innovative combinations and the quest for predictive biomarkers to optimize patient selection and treatment efficacy.