Cellular adaptation to proteotoxic stress requires rapid, multi-layered reprogramming of gene expression. To systematically decode this process, we implemented a time-resolved, multi-dimensional proteomic strategy that simultaneously profiles steady-state abundance (whole-cell proteome), real-time translation (nascent proteome), translational machinery composition (ribosomal proteome), and rapid signaling (phosphoproteome) in HeLa cells across four time points after acute heat stress. Our high-sensitivity Puromycin-Modified Silica Microsphere-based Nascent Proteomics (PMSNP) method was crucial for capturing immediate translational priorities. Multi-omics integration revealed a staged adaptive cascade. RNA splicing emerged as a central hub under multi-layered regulation: splicing factors were among the earliest translationally upregulated components, while concurrent phosphorylation fine-tuned their activity - an integrated strategy that positions the spliceosome as a rapid-response platform for stress-induced proteome remodeling. Furthermore, we uncovered a translation-coupled secretory response of IL1RAP: its synthesis was rapidly induced, accompanied by increased secretion without corresponding changes in whole-cell abundance, and functional assays established secreted IL1RAP as necessary for heat stress-induced cell migration. Notably, this secretory event coincided temporally and pathway-wise with the enrichment of “Golgi vesicle transport” in the sustained remodeling phase, suggesting it is part of a broader secretory reprogramming. This work provides a dynamic, systems-level blueprint of post-transcriptional adaptation, highlighting the power of integrated multi-dimensional proteomics to dissect how cells rewire protein expression through coordinated translational, abundance, and secretory changes in response to stress.