There isn't so much a blanket answer to this question since in some cases, we do know what has been destroyed and what the content was, thanks to finding these documents in other contexts; in some cases, we have a pretty good idea of what was destroyed and what the content was thanks to the gaps in the documentary record; and in some cases, we don't exactly know what has been destroyed and have little to no idea what the content was.

To get into some examples: The protocol of the Wannsee Conference is probably one of the most famous Nazi documents from WWII. It details a conference held in a villa at Berlin's Wannsee lake in January 1942 where under the auspices of Reinhard Heydrich of the Reich Security Main Office officials from a whole variety of government agencies discussed plans for the deportations of Jews from Europe and the way forward in dealing with so-called "mixed-race" Germans, meaning those the Nazis classified as half- and quarter-Jewish and those who had German spouses. It is, in short, a key document of the Holocaust.

Here you can find an English transcript and note how on top it says "30 copies". These were the copies distributed to the participants and kept by the Reich Security Main Office. After the war in various Allied post-war investigations, former members of the government referenced the Protocol at several points but initially no copy turned up and it looked like all had been destroyed. Until 1947 when US prosecutor in Nuremberg Robert Kempner went through a bunch of files that had been found outside of Berlin, evacuated from the Foreign Office. These files were brought to a small town in the vicinity of Berlin to save them from potential destruction through Allied bombing of the city. They included the contents of the office of former Undersecretary of the Foreign Officer, Martin Luther. Luther had in 1943 tried to instigate a coup against his superior, Ribbendrop, and subsequently been let go from his post and arrested. His files were bundled up and later evacuated. Because Luther had participated in the Wannsee Conference these files included his copy of the protocol and because they were outside of Berlin in 1945, it was saved from the destruction that had affected all other copies.

Similar examples include the Einsatzmeldungen UdSSR, meaning the collected reports of the Einsatzgruppen from the Soviet Union, the German copies of which have been destroyed but which had been intercepted by the British and collected as material important for post-war persecution or the so-called Höfle telegram. The latter is a short telegram by SS Sturmbannführer Hermann Höfle in January 1943, which gives the numbers for the Jews killed in the Aktion Reinhard Camps. Again, the German copy had been destroyed but it was discovered in 2000 in declassified British WWII material as yet another document the British had intercepted and dutifully transcribed.

Then, there are documents that we know must have existed and have a good idea about the content but that have never been found and where most likely all copies have been destroyed. The way we know about them is because documents, especially official government documents, don't exist in a vacuum. They tend to leave traces in other documents as well as in the record itself in a meta way. What I mean is that Nazi government documents f.ex. were numbered, meaning they included a reference on top about who produced the document, when it was produced and which number it had in that process. The office of Adolf Eichmann would produce documents that were numbered with "IV B 4 - 1/43" f.ex. for the first document it produced in 1943. These numbers show us obvious gaps where something is missing and sometimes, these documents are referred to in other documents, if they were produced as a response or further elaboration.

For instance, in 1943 both the Reich Security Main Office and the Foreign Office had an extensive correspondence about the treatment of Jews from Axis and neutral countries such as Sweden, Romania, Finland, and Turkey about how they should be treated resp. what should happen to them. Frequently in this correspondence, they bring up document "IV B 4 / 942/42", which is described as an early draft for these measure penned by Eichmann. Within the correspondence there are several mentions of how the new proposed measures will deviate from this early draft. A copy of the early draft doesn't exist but because it is referenced so heavily within later correspondence and its contents described in such detail, especially concerning the later deviations from the early version, we have a pretty good picture of what the early draft contained.

A similar case exists with the Generalplan Ost, which I discuss in more detail in this answer. The GPO consistent of six large documents that represented the evolving nature of the plans for "Germanization" in Eastern Europe. Two of these documents, 3 and 4, have most likely all been destroyed and their exact contents are unknown. However due to the evolving nature of these plans, later documents such as the "Comprehensive Settlement Plan" (Doc. nr. 6) reference earlier versions and documents and thus we have a picture of what they approximately contained, albeit not is as much detail as we'd like.

This is the case with a variety of documents that are referred to within later documents and through which we get a picture of what their contents were. Sometimes however, we also know that something is missing but don't have such a good idea of the exact content, only a general one. One famous example are the Wehrmacht files of individual regiments. While divisional files exist for almost every Wehrmacht division of WWII, regimental files are generally hard to come by. The reason for this is that in 1944 an Allied bomb landed on the Wehrmacht archive in Berlin and the section that burned down contained most of these files. Because the divisional files exist, we do have a picture about what the regiments were up to but due to their destruction, it can sometime be hard to ferret out specific information such as who ordered a mass execution or which regiment or company exactly carried it out.

And lastly, there are documents, we do not know about or only vaguely and where the content will most likely remain a mystery, often because whole caches or files of documents were destroyed together in 1945. These cases are rare though (at least so we think) because for a document to leave no traces at all in the overall documentary record is highly unlikely. Documents, orders, proposal etc. are how a vast machine like government communicates with its individual parts and thus, it is increasingly difficult to wipe out the traces of any comprehensive program such a government undertakes for it will always leave traces all over the record and even if sometimes the exact content of things might remain unknown due to destruction to truly leave no trace behind or remain completely hidden because of destruction is just highly unlikely.