An example of setting up a Godot scene for a Pixel game with higher resolution GUI.

pixel_game_with_gui_hd.tscn

[gd_scene load_steps=5 format=3]

[sub_resource type="Gradient" id="Gradient_8q6eo"]
offsets = PackedFloat32Array(0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1)
colors = PackedColorArray(0, 0, 0, 1, 1, 0, 0, 1, 1, 0.6, 0, 1, 0.8, 1, 0, 1, 0.2, 1, 0, 1, 0, 1, 0.4, 1, 0, 1, 1, 1, 0, 0.4, 1, 1, 0.2, 0, 1, 1, 1, 0, 0.6, 1, 1, 0, 0.0166664, 1)
metadata/_snap_enabled = true

[sub_resource type="GradientTexture2D" id="GradientTexture2D_qsl38"]
gradient = SubResource("Gradient_8q6eo")
width = 160
height = 120

[sub_resource type="FastNoiseLite" id="FastNoiseLite_nbipe"]
noise_type = 0
frequency = 0.5
fractal_type = 0

[sub_resource type="NoiseTexture2D" id="NoiseTexture2D_uwwov"]
width = 24
height = 24
generate_mipmaps = false
seamless_blend_skirt = 0.0
as_normal_map = true
bump_strength = 32.0
noise = SubResource("FastNoiseLite_nbipe")

[node name="PixelGameWithGuiHD" type="Control"]
layout_mode = 3
anchors_preset = 15
anchor_right = 1.0
anchor_bottom = 1.0
grow_horizontal = 2
grow_vertical = 2

[node name="GameLayer" type="CanvasLayer" parent="."]

[node name="AspectRatioContainer_4_3" type="AspectRatioContainer" parent="GameLayer"]
anchors_preset = 15
anchor_right = 1.0
anchor_bottom = 1.0
grow_horizontal = 2
grow_vertical = 2
ratio = 1.3333

[node name="SubViewportContainer" type="SubViewportContainer" parent="GameLayer/AspectRatioContainer_4_3"]
layout_mode = 2

[node name="SubViewport_160_120" type="SubViewport" parent="GameLayer/AspectRatioContainer_4_3/SubViewportContainer"]
handle_input_locally = false
size = Vector2i(1439, 1080)
size_2d_override = Vector2i(160, 120)
size_2d_override_stretch = true
render_target_update_mode = 4

[node name="SampleLevel" type="Node2D" parent="GameLayer/AspectRatioContainer_4_3/SubViewportContainer/SubViewport_160_120"]
texture_filter = 1

[node name="Background" type="Sprite2D" parent="GameLayer/AspectRatioContainer_4_3/SubViewportContainer/SubViewport_160_120/SampleLevel"]
texture = SubResource("GradientTexture2D_qsl38")

[node name="Character" type="Sprite2D" parent="GameLayer/AspectRatioContainer_4_3/SubViewportContainer/SubViewport_160_120/SampleLevel"]
texture = SubResource("NoiseTexture2D_uwwov")

[node name="Camera2D" type="Camera2D" parent="GameLayer/AspectRatioContainer_4_3/SubViewportContainer/SubViewport_160_120/SampleLevel/Character"]

[node name="GuiHD" type="CanvasLayer" parent="."]
layer = 2

[node name="Control" type="Control" parent="GuiHD"]
layout_mode = 3
anchors_preset = 15
anchor_right = 1.0
anchor_bottom = 1.0
grow_horizontal = 2
grow_vertical = 2