Significance Immunotherapy has revolutionized cancer treatment, yielding unprecedented long-term responses and survival. However, a significant proportion of patients remain refractory, which correlates with the absence of immune-infiltrated (“hot”) tumors. Here, we observed that FDA-approved unadjuvanted seasonal influenza vaccines administered via intratumoral injection not only provide protection against active influenza virus lung infection, but also reduce tumor growth by increasing antitumor CD8 ⁺ T cells and decreasing regulatory B cells within the tumor. Ultimately, intratumoral unadjuvanted seasonal influenza vaccine converts immunologically inactive “cold” tumors to “hot,” generates systemic responses, and sensitizes resistant tumors to checkpoint blockade. Repurposing the “flu shot” may increase response rates to immunotherapy, and based on its current FDA approval and safety profile, may be quickly translated for clinical care.