Let’s say that something within the empire just fails. The emperor simply gives out completely, but the astronomicon stays intact. Wars break out, but somewhere down the line, the inquisition and mechanicum find themselves to be in complete control over the wider imperium. Former planetary governors are replaced with members of the mechanicus or inquisition. Additionally, another war breaks out that makes these two factions merge into one single organization. Let’s just call this organization ‘the new inquisition’ or NI for short.
Unlike its predecessors, the NI does away with the dogma of the former imperium. Instead, this group hastily works to adopt all the technologies mankind currently has in mass. Surveillance and monitoring systems are so prevalent that any member of the NI can monitor the oxygen saturation levels of all its citizens at any time. The corpses of the fallen are used to nourish the embryos in vitae wombs until nearly the entire human population rebounds. However, this generation of man is equipped with sensors and connections to a wider internet that can be accessed by any of NI’s members. Information about the atrocities the soldiers and citizens under NI face is used to channel frustration and anger to all the forces of chaos, heretics, and aliens that roam the stars. Humanity’s history is taught again, but only to strengthen the interest of the organization. The age of strife is taught as a gift from NI to save humanity from alien caused extinction, the heresy is treated as a dark age caused by the emperor’s conquest over humanity, and the emergence of NI is taught as a gift to return to greatness. Within only a few years, nearly all of humanity is so heavily indoctrinated, monitored, and exploited that all signs of heresy is ultimately eradicated. Even the NI’s members aren’t able to develop any critical thought against the current progression of the new imperium. Naturally, the members of NI slowly but inevitably become fully proletarianized by the remaining members of the imperium. What drives the new imperium now is species-level hysteria and information systems dictating what the empire must accomplish. Man becomes totally enslaved to its own ideas.
Ultimately, the wars of the future become even more scary. Alien corpses are brought back to newly formed hives to be publicly mocked and shamed. Trillions of humans are spread out to new worlds to completely excavate and build new fortifications. Although technological progress grinds to a near stop, the adoptation of already existing imperial tech is used to create wars of scale and attrition analogous to the wars of feudal china. The space marines, custodes, arbiters, all those groups of special forces become utterly worthless in the face of what humanity becomes.
There truly is no way out. There is nothing to feel hope for. It’s likely that all alien life will be completely annihilated with the strength and numbers the imperium possesses at the level it is at. However, there is no way to save humanity or really intelligent life in general from ever progressing again. Inevitably, maybe thousands or millions of years, humanity dies as the last remaining living species in the wider universe. Untold numbers of planets remain shelled into oblivion, and galaxies remain empty with no sign of intelligence to ever form again.