Background: Parents often lack specific knowledge about vaccines schedules, lesser-known diseases, and vaccines safety. Enhancing parents’ knowledge about immunization is essential for informed decision-making and promoting vaccine acceptance. Objective: This systematic review aimed to identify the parents’ knowledge about immunization, including their understanding of immunization concepts, knowledge gaps, and misconceptions. The review explored the factors influencing parents’ knowledge, such as socio-demographic factors, cultural and religious beliefs, sources of information, healthcare provider communication, and vaccine hesitancy. Methods: A literature search was conducted by viewing relevant studies via computerized searching through PubMed, Scopus, and Embrace. Results: The number of reviewed studies was 137, all in English and none in Arabic. Only 47 of them were selected based on inclusion criteria. Misconceptions, such as concerns about vaccine ingredients or false associations with adverse events, contribute to vaccine hesitancy. Socio-demographic factors influence parents’ knowledge, including age, education, and income. Cultural and religious beliefs shape their understanding, and sources of information, such as healthcare providers and media, play a significant role. Conclusion: Addressing knowledge gaps and misconceptions requires strengthening healthcare provider communication, targeted educational interventions, regulation of online information, collaboration with community stakeholders, and longitudinal research.