The r5.16xlarge pairs 64 vCPU with 512 GiB of RAM, the 8.00 GiB-per-vCPU ratio that marks a memory-optimized instance. In the name, "r" stands for RAM, "5" is the generation and "16xlarge" is the size within the r5 family. It runs on Intel Xeon Platinum 8175 at 3.1 GHz, and AWS introduced it in June 2019. AWS has since shipped r6i, r7i, r8i and r9g; r6i.16xlarge is the direct replacement at this size, scoring 1,080,078 CoreMark/s against this instance's 928,658 — roughly 16% more throughput for the same vCPU count. Spot's node ladder tops out below this size, so r5.16xlarge becomes 4 × mh.vs1.2xlarge (64 vCPU, 512 GiB combined), $4.03/hr on AWS in US East (N. Virginia), from $0.084/hr on Rackspace Spot. Spot delivers compute as managed Kubernetes, so a node pool of that size is the native shape of the answer rather than a workaround — provided the workload scales horizontally.
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r5.16xlarge gives you 64 vCPU and 512 GiB in a single machine. The largest comparable Spot node, mh.vs1.2xlarge, is 16 vCPU and 128 GiB, so the equivalent here is 4 nodes rather than one.
Spot runs as managed Kubernetes, so a 4-node pool is the normal way to run things rather than a workaround. If your workload already sits behind a load balancer, a queue or a scheduler, it spreads across them without changes. If it needs all 64 cores and 512 GiB in one process, it does not.