BACKGROUND: Childhood cancer survivors have a higher risk of developing malignancies later in life compared with individuals of similar age in the general population. In Spain, population-based evidence on second malignant neoplasms (SMNs) is limited. This study aimed to estimate survival following childhood cancer diagnosis and to assess the risk of SMNs in Spain. METHODS: This population-based registry study used data from 12 cancer registries within the Spanish Network of Cancer Registries (REDECAN). All malignancies of sites and non-malignant central nervous system (CNS) tumors diagnosed before age 15 were included. Age-standardized incidence rates (ASIRw) for 2015-2019 were calculated. Five- and 10-year age-adjusted observed survival rates for 1990-1999 and 2000-2009 were estimated. SMN risk was assessed using standardized incidence ratios (SIRs) and excess absolute risks (EARs). RESULTS: The ASIRw for 2015-2019 was 181.3 per million child-years. Ten-year survival increased from 71.3% in 1990-1999 to 75.5% in 2000-2009. The overall risk of developing an SMN was significantly elevated (SIR = 5.67) at 20 years. CONCLUSIONS: Although survival for childhood cancer in Spain was around 75% in 2000-2009, childhood cancer survivors remain at substantially increased risk of SMNs for at least two decades. Efforts to reduce treatment-related toxicity while maintaining survival gains are essential.