A comprehensive multi-omics analysis of 8,286 Finnish twins reveals that stress exposure creates distinct molecular fingerprints depending on timing. Recent stress (within 6 months) triggered coordinated immune-metabolic changes, including decreased levels of five key proteins like IL-1β and TIGIT, alongside reduced HDL cholesterol and broader lipid disruptions. Lifetime stress exposure showed entirely different patterns—elevated levels of ten proteins, increased TNF/IL-10 signaling, and higher arterial aging markers. A single genetic locus on chromosome 1 (DAB1/C8B) emerged as significantly associated with stress susceptibility, specifically affecting immune T-cells and linking to cardiometabolic risk. This temporal specificity challenges assumptions that stress effects simply accumulate over time. Instead, the body appears to mount different molecular responses to acute versus chronic stress exposure, involving distinct immune, metabolic, and vascular pathways. The findings suggest personalized stress management approaches might need to consider both genetic predisposition and exposure timing. However, this preprint awaits peer review, and the observational design cannot establish whether these molecular changes directly cause health outcomes or represent adaptive responses. The research represents a significant advance in understanding stress biology's complexity.