The ongoing monkeypox (MPX) outbreak has been declared a public health emergency of international concern. People in close contact with active MPX cases, including healthcare workers (HCWs), are at higher risk of virus acquisition since the MPX virus can be transmitted by skin contact or respiratory secretions. In this study, we aimed to assess the psychological antecedents of MPX vaccination among Nigerian HCWs using the 5C scale. We used an anonymous online cross-sectional survey to recruit potential participants using snowball sampling. The questionnaire aimed to assess the geo/socioeconomic features and the 5C psychological antecedents of vaccine acceptance (confidence, complacency, constraints, calculation, and collective responsibility). A total of 389 responses were included, with a median age of 37 years (IQR: 28–48), 55.5% males, and 60.7% married participants. Among the studied Nigerian HCWs, only 31.1% showed confidence in MPX vaccination, 58.4% expressed complacency towards vaccination, 63.8% perceived constraints towards MPX vaccination, 27.2% calculated the benefits and risks of vaccination, and 39.2% agreed to receive MPX vaccination to protect others. The determinants of MPX vaccine confidence were being single (OR = 5.07, 95% CI: 1.26–20.34, p = 0.022), a higher education level (with pre-college/high school as a reference, professional/technical: OR = 4.12, 95% CI: 1.57–10.73, p = 0.004, undergraduate: OR = 2.94, 95% CI: 1.32–6.55, p = 0.008, and postgraduate degree (OR = 3.48, 95% CI: 1.51–8.04, p = 0.003), and absence of chronic disease (OR = 2.57, 95% CI: 1.27–5.22, p = 0.009). The significant complacency predictors were having a middle-income (OR = 0.53, 95% CI: 0.33–0.89, p = 0.008), having a bachelor’s degree (OR = 2.37, 95% CI: 1.10–5.11, p = 0.027), and knowledge of someone who died due to MPX (OR = 0.20, 95% CI: 0.05–0.93, p = 0.040). Income was associated with perceived vaccination constraints (OR = 0.62, 95% CI: 0.39–0.99, p = 0.046). Participants aged 46–60 years had decreased odds in the calculation domain (OR = 0.52, 95% CI: 0.27–0.98, p = 0.044). Middle-income and bachelor degree/postgraduate education significantly influenced the collective responsibility domain (OR = 2.10, 95% CI: 1.19–3.69, p = 0.010; OR = 4.17, 95% CI: 1.85–9.38, p < 0.001; and OR = 3.45, 95% CI: 1.50–7.90, p = 0.003, respectively). An investigation of the 5C pattern-based psychological antecedents of MPX vaccination in a sample of Nigerian HCWs revealed low levels of vaccine confidence and collective responsibility with high levels of constraints and complacency. These psychological factors are recommended to be considered in any efforts aiming to promote MPX vaccination needed in a country where MPX is endemic.