Macropinocytosis is a conserved endocytic pathway, for the voluminous uptake of fluids and particles, that is inducible in most cell types but also occurs constitutively in macrophages for immune surveillance and in cancer cells for nutrient acquisition. In macrophages we have shown that cell surface ruffles, filopodia and macropinosomes are discrete signalling sites, defined by transient phospholipids, cholesterol-rich microdomains and ability to attract signalling kinases at the behest of activated Toll-like receptors to drive transcription and release of inflammatory cytokines. A suite of Rab GTPases is recruited to bring about ruffle formation and macropinocytosis for this signalling function. In human breast cancer cells some of the same Rab GTPases, namely members of the Rab8 subfamily, are recruited for similar functions. Through 4D lattice light sheet microscopy (LLSM) and AI we can perform quantitative analysis of ruffles and filopodia, mechanistically equating actin-mediated ruffle size and subsequent macropinosome size and number to the activation of specific Rabs. In cultures, cancer spheroids and tumour samples, increased Rab-mediated macropinocytic uptake is enhanced in nutrient-deprived environments, correlating with protein uptake and proliferation to support metastatic cancers. Upregulated gene expression of specific Rabs is required for enhanced macropinocytosis to support the growth of aggressive cancer cells, while loss of GTPase function prevents growth of these cells. Varying the size and number of macropinosomes in immune cells has dramatic outcomes in signalling for inflammation and in metastatic, fast-growing cancer cells, macropinosome size and number directly control cell survival and tumour growth.