The high prevalence of health conditions among U.S. women receiving Temporary Assistance for Needy Families (TANF, or 'welfare') impedes the ability of many in this group to move from 'welfare-to-work', and the economic recession has likely exacerbated this problem. Despite this, few interventions have been developed to improve employment outcomes by addressing the health needs of women receiving TANF, and little is known about the impact of economic downturns on the employment trajectory of this group. Using data from a recent randomized controlled trial (RCT) that tested the efficacy of a public health nursing (PHN) intervention to address the chronic health condition needs of 432 American women receiving TANF, we examine the effect of the intervention and of recession exposure on employment. We further explore whether intervention effects were modified by select sociodemographic and health characteristics. Both marginal and more robust intervention effects were noted for employment-entry outcomes (any employment, p = 0.05 and time-to-employment, p = 0.01). There were significant effects for recession exposure on employment-entry (any employment, p = 0.002 and time-to-employment, p < 0.001). Neither the intervention nor recession exposure influenced longer-term employment outcomes (employment rate or maximum continuous employment). Intervention effects were not modified by age, education, prior TANF receipt, functional status, or recession exposure, suggesting the intervention was equally effective in improving employment-entry across a fairly heterogeneous group both before and after the recession onset. These findings advance our understanding of the health and employment dynamics among this group of disadvantaged women under variable macroeconomic conditions, and have implications for guiding health and TANF-related policy.