On my laptop, I am running full disk encryption (LUKS with a single encrypted ext4 partition), and a single, large swap file as large as my system RAM (16GB).

Here's how to make it work:

Make your swapfile have at least the size of your systems RAM:

sudo swapoff /swapfile
sudo dd if=/dev/zero of=/swapfile bs=$(cat /proc/meminfo | grep MemTotal | grep -oh '[0-9]*') count=1024 conv=notrun
sudo mkswap /swapfile
sudo swapon /swapfile

Note the UUID of the partiton containing your swapfile:

$ sudo findmnt -no SOURCE,UUID -T /swapfile
/dev/nvme0n1p5 20562a02-cfa6-42e0-bb9f-5e936ea763d0

Reconfigure the package uswsusp correctly:

sudo apt -y install uswsusp
sudo dpkg-reconfigure -pmedium uswsusp
# Answer "Yes" to continue without swap space
# Select "/dev/disk/by-uuid/20562a02-cfa6-42e0-bb9f-5e936ea763d0" replace the UUID with the result from the previous findmnt command
# Encrypt: "No"

Edit the SystemD hibernate service using sudo systemctl edit systemd-hibernate.service and fill it with the following content:

[Service]
ExecStart=
ExecStartPre=-/bin/run-parts -v -a pre /lib/systemd/system-sleep
ExecStart=/usr/sbin/s2disk
ExecStartPost=-/bin/run-parts -v --reverse -a post /lib/systemd/system-sleep

Note the offset of your swapfile relative to the partition start:

$ sudo swap-offset /swapfile
resume offset = 34818

Tell grub to resume by editiing your etc/default/grub

GRUB_CMDLINE_LINUX_DEFAULT="resume=UUID=20562a02-cfa6-42e0-bb9f-5e936ea763d0 resume_offset=34818 quiet splash"

Update grub:

sudo update-grub

Create /etc/initramfs-tools/conf.d/resume

RESUME=UUID=20562a02-cfa6-42e0-bb9e-5e936ea763d0 resume_offset=34816
# Resume from /swapfile

Update initramfs:

sudo update-initramfs -u -k all

Now you can just hibernate your system with

sudo systemctl hibernate