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It really depends on what you're doing exactly, but there are some things i'd check right away. first of all see if you're querying the database without indexes - that's one of the most common causes of slowdowns. if you use mongodb check that your find() calls have the right indexes, same thing with postgresql. then look if you're doing too many synchronous operations when you could be using async/await properly, maybe you're loading entire files into memory when you could be streaming, or you're doing n+1 queries when one with a join would be enough. another thing: if you use express make sure you don't have useless middleware or middleware doing heavy operations unnecessarily.
then i'd say do real profiling, not just guessing. use node --prof to generate an isolate file, then analyze it with node --prof-process. or use clinic.js which is easier to read, or just throw console.time() around your code to see where time is spent. sometimes you discover the bottleneck is where you'd least expect it, like some library you installed that does something heavy behind the scenes. if you're doing a lot of heavy computations also think about worker threads to avoid blocking the event loop.
oh and obviously, update node to a stable version if you're behind, make sure you have enough memory available and that you're not leaking memory (monitor with process.memoryUsage()). sometimes the problem isn't even the code but your hosting configuration or the number of db connections you're opening. start with profiling and from there you'll understand what's actually eating up your resources.
True, database indexes are fundamental, but from a code mechanics perspective I can tell you that often the problem is also at the application level - like if you're doing heavy synchronous operations on the main thread, node gets blocked and everything slows down. Try profiling with `node --prof` to see where you're spending time, and if you find heavy bottlenecks move everything to worker threads or switch to asynchronous operations with async/await instead of badly chained promises. Also npm dependencies sometimes are a disaster - check if you have any particularly bloated ones you can replace, because I've seen a lot of people carrying around libraries that do things you could solve in a few lines.
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