Early-life adversities are a major risk factor for later mental health disorders, but the neurobiological mechanisms remain poorly understood. To address this gap, we established a multidimensional murine model of social and material deprivation (SMD) that combines reduced nesting, maternal separation, early weaning, and exposure to social stress. This paradigm aims to better reproduce the complexity of socioeconomic disadvantage in humans. Offspring exposed to SMD model displayed delayed growth, heightened anxiety- and depression-like behaviors, increased aggression, and impaired social cognition. Structural analyses revealed reductions in dorsal and ventral hippocampal area, along with an enlargement of the prefrontal cortex. Transcriptomic profiling of the prefrontal cortex uncovered sex-specific signatures: males showed upregulation of genes linked to neuronal development and immune function, while females exhibited increased expression of chromatin remodeling genes and downregulation of immune-related pathways. Altogether, these findings indicate that SMD disrupts brain development and social behavior through sex-dependent molecular mechanisms, with neuroinflammation and epigenetic regulation emerging as potential contributors.