In the current study, common and unique genetic and environmental influences on personality and a broad range of well-being measures were investigated. Data on the Big Five, life satisfaction, quality of life, self-rated health, loneliness, and depression from 14,253 twins and their siblings (age M: 31.82, SD: 14.41, range 16–97) from the Netherlands Twin Register were used in multivariate extended twin models. The best-fitting theoretical model indicated that genetic variance in personality and well-being traits can be decomposed into effects due to one general, common factor ( Mdn: 60%, range 15%–89%), due to personality-specific ( Mdn: 2%, range 0%–78%) and well-being-specific ( Mdn: 12%, range 4%–35%) factors, and trait-specific effects ( Mdn: 18%, range 0%–65%). Significant amounts of non-additive genetic influences on the traits’ (co)variances were found, while no evidence was found for quantitative or qualitative sex differences. Taken together, our study paints a fine-grained, complex picture of common and unique genetic and environmental effects on personality and well-being. Implications for the interpretation of shared variance, inflated phenotypic correlations between traits and future gene finding studies are discussed.