Despite the significant progress in targeted therapies for melanoma, advanced stage metastatic melanoma is still currently incurable. This highlights the urgent need for novel therapeutics that specifically act to inhibit metastasis - known as ‘migrastatics’. Further, suitable migrastatic targets can only be uncovered by studying and elucidating the mechanisms and biology that drive metastatic melanoma. It is widely understood that the cell motility underlying invasion is driven by the orchestration of various elements of the cell cytoskeleton, identifying these proteins as key targets. Additionally, the modality that cancer cells employ to undergo invasion is highly dependent on the bio-chemical composition of the micro-environment, which underscores why metastatic disease is regarded as a heterogeneous disease state. This adaptability of cancer cell motility arises through a cellular process of ‘mechanosensing’, whereby the bio-chemical properties of the extracellular matrix can influence the spatiotemporal regulation of cell adhesion-cytoskeletal crosstalk to influence cell migration. Here, we report that the protein Cytoskeletal Linker ASsociated Protein or CLASP, that has functions to tether and stabilise microtubules, are highly expressed in a panel of melanoma cell lines. Further, melanoma cells utilise 2 unique paralogs of CLASP for differing functions to drive 3D invasion. Using fluorescent tagging and quantitative live cell imaging approaches, we report that the selective depletion of CLASP paralogs in 1205Lu melanoma cells abrogates invasion by interfering with crucial microtubule-dependent functions during 3D-invasion. Further pan-depletion of CLASPs within 1205Lu melanoma cells results in 3D migration-stasis and reduced cell viability when cells are exposed to conditions of 3D confinement. These findings suggest that the microtubule associated protein, CLASP, functions in melanoma cells to facilitate cellular processes of both invasion and survival.