Background Despite the success of childhood vaccination in reducing vaccine-preventable diseases (VPDs), vaccine hesitancy remains a significant challenge in several countries, such as Saudi Arabia, both during and beyond the COVID-19 era. Furthermore, the pandemic may have impacted vaccine hesitancy trends, potentially affecting parents' intentions to adhere to scheduled childhood vaccination programs. Aim This article aims to assess the extent of parents' hesitancy towardchildhood vaccination, determine if it increased or decreased due to the COVID-19 pandemic, highlight the factors and determinants that influenced this hesitancy, whether positively or negatively, during the COVID-19 era, andestimate the acceptance of COVID-19 vaccination in relation to the acceptance of scheduled childhood vaccination. Methods A cross-sectional study was conducted in Saudi Arabia through a snowball sampling technique. Data were collected between September 2022 and October 2022 using an online survey using Google Forms. The inclusion criteria were parents or guardians in Saudi Arabia with a child up to 18 years of age.Responses were analyzed using SPSS V25 (IBM Corp., Armonk, NY, US), with chi-square tests and logistic regression performed to compare hesitancy and vaccination status. Results Among the 1,209 parents and care providers who participated, the prevalence of parents' vaccine hesitancy was 374 (30.9%). The educational level of the parents was not significantly associated with hesitancy status (p 0.490). The most refused vaccine was Mpox (345; 28.5%), whereas the one that caused the most hesitancy was the COVID-19 vaccine (352; 29.1%). Regarding the parents' concerns, the main reason for their hesitancy was the influence of their negative perceptions from social media content, including false or misleading information and negative allegations about vaccines, reported by 449 (18.98%) of the participants. Logistic regression analysis indicated that negative social media perceptions significantly increased the likelihood of vaccine hesitancy (OR = 2.15, 95% CI = 1.78-2.60, p < 0.001). Conclusion Our study highlights the prevalence of parental vaccine hesitancy during the COVID-19 era; the most significant hesitancy was observed towardthe COVID-19 vaccine, and the mpox vaccine was the most rejected. Negative social media was the main reason for parental hesitancy; public health efforts should focus on providing accurate and easily accessible information through educational campaigns on social media and other platforms.