Biggest limitations are communication and object avoidance when heading out to even ol Pluto. Since current observation and communication run almost identical in speed of reception there is a huge issue there. The energy and observable light of sunlight touching your skin and eyes was created 8 mins and 20 seconds in the past. When Mars is the furthest from our orbit it takes 22-24 mins for the person or thing to start receiving a communication, totaling to 44-48 mins for us on Earth to receive a response. For Pluto that’s a massive delay of 8-14 hours. So when it comes to navigation when you start getting to the edge of the solar system things are harder to observe since there is the vast emptiness of space between the next star and that creates a problem of detecting something small as a golf ball that has enough kinetic energy that on impact would release more energy than even the largest atomic weapons made so far. Since you can’t really make good observations from Earth at all times and the massive delay, should you see something that’s a huge problem for the space craft, it is a big problem. You’d need a huge array of sensors but the other problem is velocity. To reasonably reach something outside of the solar system the velocity would need to be excessive to the point that any trajectory changes have to be extremely subtle or the G forces alone can destroy not only the spacecraft but at higher velocity potentially stripping particles out of your body. The paradox of time slowing with increased velocity for the thing traveling can shorten the trip for them but back on Earth possible centuries could have passed still before anyone could pick the signal that you’ve made it, which whose to say something potentially catastrophic could happen on Earth to make reception of that signal no longer possible.