Abstract The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier-stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities. The direct injection of immune stimulating agents into the tumor primes the local tumor-specific immunity to generate a systemic, durable clinical response. Intratumoral immunotherapy is a highly active area of investigation resulting in a plethora of agents, for example, immune receptor agonists, non-oncolytic and oncolytic viral therapies, being tested in preclinical and clinical settings. Currently, more than 20 neoadjuvant clinical trials exploring distinct intratumoral immune stimulatory agents and their combinations are ongoing. Practical considerations, including appropriate timing and optimal local delivery of immune stimulatory agents play an important role in safety and efficacy of this approach. Here, we discuss promising approaches in drug delivery technologies and opportunity for combining intratumoral immunotherapy with other cancer treatments and summarize the recent preclinical and clinical evidences that highlighted its promise as a part of routine oncologic care.