Immunotherapy and cancer vaccines are showing varied clinical results. Pfizer’s antibody-drug conjugate Padcev, combined with Merck’s Keytruda, demonstrated meaningful survival benefits in bladder cancer patients unable to receive chemotherapy, prompting regulatory discussions for expanded indications. Conversely, IO Biotech’s off-the-shelf melanoma vaccine narrowly missed its primary endpoint in a Phase 3 trial, though subgroup analyses suggest potential benefit. Additionally, researchers have discovered novel resistance mechanisms and therapeutic targets in breast and triple-negative breast cancer, offering pathways to enhance immunotherapy efficacy. This spectrum reflects challenges and opportunities in advancing cancer immunotherapy.