I wouldn’t say a game being unpopular will stop a re-release .
These boutique companies will release any old shit as long as the IP is cheap enough. They’ve already done it on a number of occasions.
Peripheral requirements is a big one, especially all those DS games that used the GBA expansion slot. Even if a game can be rereleased, the complete experience may not be preserved without robust peripherals support. The mini console boom at least graced us with the Taito Egret Mini and its paddle controller.
Games tied to esoteric hardware is another category…the amount of work to translate a PSP or DS game to HD systems restricts the pool of games that may see a rerelease to the biggest sellers only. The alternative is an emulation solution but even the latest DS Castlevania Collection isn’t an ideal way to present the games. Even a traditional game like Kid Icarus: Uprising can’t come back because it was designed around inertia in its aiming system - something you can’t replicate with an analogue stick, gyro, or mouse controls.
Changing perceptions in content is another barrier, hence Mother 3 never releasing outside Japan at its release and even in the digital age where the risk of distributing physical games has evaporated. While a western release of Mother 3 has a proven audience to sell to, Nintendo seems keen to distance itself from the game likely due to its controversial themes. With platform holders now imposing their own standards on content above and beyond each country’s ratings boards, there are many retro titles that are unlikely to see modern releases, or unadultered modern releases. Some of these games are only a decade old, like Spike Chunsoft’s Danganronpa: Ultra Despair Girls.
Games with licensed content - moving beyond music, licensed vehicles seems to be posing a headache for the return of many games where you drive or pilot cars, planes, etc. The most famous example may end up being the Forza Horizon series, where older titles have long been delisted and will never return as publisher Microsoft wants players on the latest game. But a plethora of rally games, driving games, flight simulators and arcade titles have been lost to time because of this. Alternatively, it will also mean games return with adjustments - see Sega’s rereleases of Out Run removing the Ferrari Testarossa. Out Run 2’s has more cars, and more detailed graphics, making such an adjustment untenable. The game remains unrevived to this day.
Older games that compete with the new. I’d love Nintendo to bring back Mario Kart Wii, because it plays so differently to the newer games. But with the latest games being sales juggernauts, Nintendo wouldn’t even consider it. Likewise the sheer size of Sony’s hollywood blockbusters means they have chosen to focus on core IP cultivated during the PS3/4 era. The likelihood of Sony going back to republish the esoteric portions to its back catalogue remains slim.