Importance Firearms are the leading cause of death for children and adolescents in the United States. While mass shootings and community gun violence draw significant media attention, little research explores pediatric in-home homicide. Objective To analyze pediatric firearm homicides by location and sociodemographic characteristics. We hypothesized that young children are most likely to die by in-home firearm homicide. Design, Setting, and Participants This retrospective cohort study used data from the National Violent Death Reporting System Restricted Access Database, including 48 states and the District of Columbia from 2020 and 2021 and 14 states from 2005 through 2021. Child and adolescent victims of firearm-related homicide aged 0 to 17 years were included. Data were analyzed between September 13, 2024, and June 28, 2025. Exposure Age and child developmental stage. Main Outcome and Measures The main outcome was in-home homicide vs homicide elsewhere. Multivariable logistic regression was used to assess characteristics associated with in-home pediatric homicide. Temporal trends were assessed with linear regression. Results Among 2196 pediatric firearm-related homicides from 2020 through 2021, victims’ median (IQR) age was 16 (14-17) years. Overall, 1790 (81.5%) were male and 406 (18.5%) were female. Of these homicides, 24.4% (n = 536) occurred at home and 75.6% (n = 1660) occurred outside the home. For younger children (aged 0-12 years; n = 391), 63.2% (n = 247) of firearm-related homicides occurred at home. Each 1-year increase in age was associated with a decrease in the odds of homicide occurring at home vs elsewhere (adjusted odds ratio, 0.83; 95% CI, 0.81-0.85; P &lt; .001). Compared with firearm-related homicides occurring outside the home, in-home homicides were more often associated with murder-suicide (23.0% [n = 123] vs 1.6% [n = 27]; P &lt; .001), child abuse (20.1% [n = 108] vs 2.3% [n = 38]; P &lt; .001), and intimate partner violence (16.8% [n = 90] vs 2.4% [n = 40]; P &lt; .001). Of the 310 in-home homicides for which the assailant relationship was identified, a parent was reported in 41.6% (n = 129), an acquaintance in 18.1% (n = 56), a sibling in 13.5% (n = 42), and a parent’s intimate partner in 11.3% (n = 35). From 2005 through 2021, the incidence of in-home homicide increased from its lowest rate of 0.18 homicides per 100 000 children and adolescents in 2010 to 0.38 homicides per 100 000 in 2021 (β, 0.02; 95% CI, 0.01-0.03; P &lt; .001). Conclusions and Relevance This study found that nearly one-quarter of pediatric firearm-related homicides occurred at home. Young children were more often affected. These data point to domestic violence and child abuse as significant risk factors for in-home firearm homicide. Traditional safe storage laws may be inadequate preventive measures. Extreme risk protection orders and mandatory domestic violence–related firearm relinquishment may prevent these deaths and warrant further investigation.