Happiness is receiving more and more interest both as a determinant of health and a measure of outcome in biomedical and psychological sciences. The main objective of this study was to assess how the levels of happiness vary in a large sample of Italian adults and to identify the socio-demographic conditions which impair happiness domains the most. The participants of this survey consisted of 1695 Italian adults (85.9% women; 14.1% men) who completed the Measure of Happiness (MH) questionnaire online. In this study, the differences between groups in total and single domain (life perspective, psychophysical status, socio-relational sphere, relational private sphere, and financial status) happiness levels were examined through a propensity score matching analysis with respect to socio-demographic conditions, including gender, age, annual income, relationship status, having children, and education level. The results show that low income has a negative impact on happiness levels, whereas being in a relationship has a positive effect. Having children appears to have a negative impact on male happiness. Males appear to be happier than females, especially with regard to the psychophysics status. This evidence emphasizes the urgency for Italian policymakers to take actions on removing obstacles to people’s happiness, especially with regard to financial distress, parenthood, and gender gaps.